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Akbarzadeh AR, Borzouei S, Khazaei S, Jazaeri M. Evaluation of the Relationship Between Salivary Adipokine Levels With Appetite and Anthropometric Indices in Patients With Type 2 Diabetes. Endocrinol Diabetes Metab 2024; 7:e70012. [PMID: 39539026 PMCID: PMC11561133 DOI: 10.1002/edm2.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 10/04/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
OBJECTIVE This study aimed to evaluate the association between salivary adipokine levels, including leptin, chemerin, resistin and interleukin-6, with body mass index (BMI), waist and wrist circumference and appetite in patients with type 2 diabetes. METHODS In this cross-sectional study, 104 participants were divided into three groups: 35 diabetic patients, 35 pre-diabetic individuals and 34 healthy controls. Unstimulated saliva samples were collected using the spitting method, and salivary levels of leptin, chemerin, resistin and interleukin-6 were measured via ELISA. Appetite was assessed using a standard questionnaire, and BMI, waist and wrist circumferences were measured with a tape measure. Statistical analysis was performed using SPSS 26, with a significance threshold set at 0.01. RESULTS Significant differences were found in the salivary levels of leptin, chemerin, and resistin among the three groups (p < 0.01), but no significant difference was observed in the salivary levels of interleukin-6 (p > 0.01). Analysis also revealed significant differences in appetite traits among the groups, with the highest appetite trait observed in pre-diabetic subjects (p = 0.0002). The salivary level of chemerin was significantly associated with appetite traits regardless of diabetic status (p = 0.009). Appetite was also significantly related to BMI (p = 0.002) and waist circumference (p = 0.001) in all subjects. However, no significant relationship was observed between appetite and fasting plasma glucose or HbA1c levels (p > 0.01). CONCLUSION The results of this study indicate that salivary levels of certain adipokines, such as leptin, chemerin and resistin, may be significantly higher in diabetic patients, although this is not true for all adipokines. While pre-diabetic patients exhibited a higher level of appetite, no positive correlation was found between salivary adipokine levels (except chemerin) and appetite or anthropometric characteristics, irrespective of diabetic status.
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Affiliation(s)
- Amir Reza Akbarzadeh
- Department of Oral and Maxillofacial Medicine, Dental Research Center, School of DentistryHamadan University of Medical SciencesHamadanIran
| | - Shiva Borzouei
- Endocrinology & Metabolism, Department of Internal Medicine, School of MedicineHamadan University of Medical SciencesHamadanIran
| | - Salman Khazaei
- Epidemiology, Department of Epidemiology, School of HealthHamadan University of Medical SciencesHamadanIran
| | - Mina Jazaeri
- Oral & Maxillofacial Medicine, Department of Oral and Maxillofacial Medicine, Dental Research Center, School of DentistryHamadan University of Medical SciencesHamadanIran
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Maranesi M, Palmioli E, Dall'Aglio C, Marini D, Anipchenko P, De Felice E, Scocco P, Mercati F. Resistin in endocrine pancreas of sheep: Presence and expression related to different diets. Gen Comp Endocrinol 2024; 348:114452. [PMID: 38246291 DOI: 10.1016/j.ygcen.2024.114452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 12/30/2023] [Accepted: 01/14/2024] [Indexed: 01/23/2024]
Abstract
Resistin (RETN), a recently discovered adipokine, is a cysteine-rich and secretory protein produced by adipocytes. RETN has been detected in several tissues, including human and laboratory animals' pancreas, wherein impairs glucose tolerance and insulin (INS) action and causes INS resistance. This study aims to evaluate the presence and expression of RETN in the pancreas of 15 adult female sheep reared on Apennine pastures, which show a decrease in their nutritional value due to the drought stress linked to the increasing summer aridity. The sheep were divided into 3 groups according to the diet they were subjected to: maximum pasture flowering (MxF) group, maximum pasture dryness (MxD) group, and experimental (Exp) group which received a feed supplementation in addition to the MxD group feeding. Immunohistochemistry and immunofluorescence were performed on formalin-fixed and paraffin-embedded sections of the pancreas to detect the RETN presence and to evaluate the co-localization of RETN with both glucagon (GCG)- and INS-producing cells. In addition, the expression of the three molecules was evaluated also in relation to different diets. RETN was observed only in the endocrine pancreas, showing a wide distribution throughout the pancreatic islets with few negative cells and the RETN producing cells colocalized with both α cells and ß cells. No differences in distribution and immunostaining intensity of RETN, GCG and INS were observed among the three groups. Quantitative PCR showed the expression of RETN, GCG and INS in all tested samples. No significant differences were observed for RETN and GCG among all three groups of sheep. Instead, a high statistically significant expression of INS was detected in the MxF group with respect to the Exp and MxD groups. These results highlight the localization of RETN in GCG- and INS-secreting cells involved in glucose homeostasis suggesting a modulatory role for RETN. Furthermore, the RETN expression is not influenced by food supplementation and thus is not affected by diet.
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Affiliation(s)
- Margherita Maranesi
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy.
| | - Elisa Palmioli
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy; Department of Philosophy, Social Sciences, and Education, PhD Course in "Ethics of Communication, Scientific Research and Technological Innovation" Medical-Health Curriculum, University of Perugia, Piazza G. Ermini, 1, 06123 Perugia, IT, Italy.
| | - Cecilia Dall'Aglio
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy.
| | - Daniele Marini
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy; Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18A, 752 36 Uppsala, Sweden.
| | - Polina Anipchenko
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy.
| | - Elena De Felice
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Pontoni 5, 62032 Camerino, IT, Italy.
| | - Paola Scocco
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Pontoni 5, 62032 Camerino, IT, Italy.
| | - Francesca Mercati
- Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, IT, Italy.
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Sato S. Adipo-oncology: adipocyte-derived factors govern engraftment, survival, and progression of metastatic cancers. Cell Commun Signal 2024; 22:52. [PMID: 38238841 PMCID: PMC10797898 DOI: 10.1186/s12964-024-01474-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 01/03/2024] [Indexed: 01/22/2024] Open
Abstract
Conventional therapies for metastatic cancers have limited efficacy. Recently, cancer therapies targeting noncancerous cells in tumor microenvironments have shown improved clinical outcomes in patients. However, further advances in our understanding of the metastatic tumor microenvironment are required to improve treatment outcomes. Adipocytes are distributed throughout the body, and as a part of the metastatic tumor microenvironment, they interact with cancer cells in almost all organs. Adipocytes secrete various factors that are reported to exert clinical effects on cancer progression, including engraftment, survival, and expansion at the metastatic sites. However, only a few studies have comprehensively examined their impact on cancer cells. In this review, we examined the impact of adipocytes on cancer by describing the adipocyte-secreted factors that are involved in controlling metastatic cancer, focusing on adipokines, such as adiponectin, leptin, visfatin, chemerin, resistin, apelin, and omentin. Adipocyte-secreted factors promote cancer metastasis and contribute to various biological functions of cancer cells, including migration, invasion, proliferation, immune evasion, and drug resistance at the metastatic sites. We propose the establishment and expansion of "adipo-oncology" as a research field to enhance the comprehensive understanding of the role of adipocytes in metastatic cancers and the development of more robust metastatic cancer treatments.
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Affiliation(s)
- Shinya Sato
- Morphological Analysis Laboratory, Kanagawa Cancer Center Research Institute, 2-3-2, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan.
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan.
- Department of Pathology, Kanagawa Cancer Center Hospital, 2-3-2, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan.
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Oikonomou P, Nikolaou C, Papachristou F, Sovatzidis A, Lambropoulou M, Giouleka C, Kontaxis V, Linardoutsos D, Papalois A, Pitiakoudis M, Tsaroucha A. Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats. MEDICINA (KAUNAS, LITHUANIA) 2023; 60:74. [PMID: 38256335 PMCID: PMC10820626 DOI: 10.3390/medicina60010074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/30/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024]
Abstract
Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.
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Affiliation(s)
- Panagoula Oikonomou
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Christina Nikolaou
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Fotini Papachristou
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Apostolos Sovatzidis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Maria Lambropoulou
- Laboratory of Histology-Embryology, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Charikleia Giouleka
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Vasileios Kontaxis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Dimitrios Linardoutsos
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Apostolos Papalois
- Experimental Research Center, ELPEN Pharmaceuticals, Pikermi, 19009 Athens, Greece;
| | - Michael Pitiakoudis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Alexandra Tsaroucha
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
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Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study. J Pers Med 2022; 12:jpm12050735. [PMID: 35629157 PMCID: PMC9143828 DOI: 10.3390/jpm12050735] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 04/20/2022] [Accepted: 04/26/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Sedentary lifestyles, urbanization and improvements in socio-economic status have had serious effects on the burden of diabetes across the world. Diabetes is one of the 10 leading causes of death globally, and individuals with diabetes have a 2–3-fold increased risk of all-cause mortality. Adipose tissue is increasingly understood as a highly active endocrine gland that secretes many biologically active substances, including adipocytokines. However, the exact and discrete pathophysiological links between obesity and T2DM are not yet fully elucidated. Methods: In the current study, we present the association of five diverse adipocytokines, adiponectin, leptin, resistin, visfatin and chemerin, with T2DM in 87 patients (46 males and 41 females) with type 2 diabetes mellitus and 85 healthy controls (44 males and 41 females) from the Asir region of Saudi Arabia. The patients were divided into four groups: normal BMI, overweight, obese and severely obese. The baseline biochemical characteristics, including HbA1c and anthropometric lipid indices, such as BMI and waist–hip ratio, were determined by standard procedures, whereas the selected adipokine levels were assayed by ELISA. Results: The results showed significantly decreased levels of adiponectin in the T2DM patients compared to the control group, and the decrease was more pronounced in obese and severely obese T2DM patients. Serum leptin levels were significantly higher in the females compared to the males in the controls as well as all the four groups of T2DM patients. In the male T2DM patients, a progressive increase was observed in the leptin levels as the BMI increased, although these only reached significantly altered levels in the obese and severely obese patients. The serum leptin levels were significantly higher in the severely obese female patients compared to the controls, patients with normal BMI, and overweight patients. The leptin/adiponectin ratio was significantly higher in the obese and severely obese patients compared to the controls, patients with normal BMI, and overweight patients in both genders. The serum resistin levels did not show any significant differences between the males and females in thr controls or in the T2DM groups, irrespective of the BMI status of the T2DM patients. The visfatin levels did not reveal any significant gender-based differences, but significantly higher levels of visfatin were observed in the T2DM patients, irrespective of their level of obesity, although the higher values were observed in the obese and highly obese patients. Similarly, the serum chemerin levels in the controls, as well as in T2DM patients, did not show any significant gender-based differences. However, in the T2DM patients, the chemerin levels showed a progressive increase, with the increase in BMI reaching highly significant levels in the obese and severely obese patients, respectively. Conclusion: In summary, it is concluded that significantly altered concentrations of four adipokines, adiponectin, leptin, visfatin and chemerin, were found in the T2DM patient group compared to the controls, with more pronounced alterations observed in the obese and highly obese patients. Thus, it can be surmised that these four adipokines play a profound role in the onset, progression and associated complications of T2DM. In view of the relatively small sample size in our study, future prospective studies are needed on a large sample size to explore the in-depth relationship between adipokines and T2DM.
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Abdalla MMI. Salivary resistin level and its association with insulin resistance in obese individuals. World J Diabetes 2021; 12:1507-1517. [PMID: 34630903 PMCID: PMC8472494 DOI: 10.4239/wjd.v12.i9.1507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 05/11/2021] [Accepted: 07/15/2021] [Indexed: 02/06/2023] Open
Abstract
The escalating global burden of type 2 diabetes mellitus necessitates the implementation of strategies that are both more reliable and faster in order to improve the early identification of insulin resistance (IR) in high-risk groups, including overweight and obese individuals. The use of salivary biomarkers offers a promising alternative to serum collection because it is safer, more comfortable, and less painful to obtain saliva samples. As obesity is the foremost contributory factor in IR development, the adipocytokines such as leptin, adiponectin, resistin, and visfatin secreted from the adipose tissue have been studied as potential reliable biomarkers for IR. Measurement of salivary adipokines as predictors for IR has attracted widespread attention because of the strong correlation between their blood and salivary concentrations. One of the adipokines that is closely related to IR is resistin. However, there are conflicting findings on resistin's potential role as an etiological link between obesity and IR and the reliability of measuring salivary resistin as a biomarker for IR. Hence this study reviewed the available evidence on the potential use of salivary resistin as a biomarker for IR in order to attempt to gain a better understanding of the role of resistin in the development of IR in obese individuals.
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Weaver JR, Odanga JJ, Breathwaite EK, Treadwell ML, Murchinson AC, Walters G, Fuentes DP, Lee JB. An increase in inflammation and islet dysfunction is a feature of prediabetes. Diabetes Metab Res Rev 2021; 37:e3405. [PMID: 33463010 DOI: 10.1002/dmrr.3405] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 03/26/2020] [Accepted: 08/18/2020] [Indexed: 12/24/2022]
Abstract
AIMS Type 2 diabetes (T2D) is a global health problem that will be diagnosed in almost 300 million people by 2025 according to the World Health Organization. Before being diagnosed with T2D, individuals may have glucose levels above normal but below the diabetic range. This condition is known as prediabetes. Studies showed that people with prediabetes had an increase in several pro-inflammatory cytokines in their serum and in their fasting glucose levels. The answer remains unclear when inflammation begins in the pancreas and islets, and what is the extent of this inflammation. METHODS Subjects with haemoglobin A1c levels from 5.7% to 6.4% were classified as pre-diabetic. Sections of pancreas and isolated islets from normal donors and donors with prediabetes were tested for markers of inflammation and glucose-stimulated insulin secretion (GSIS). RESULTS Gene and protein expression of the inflammatory markers resistin, interleukin-1 beta, tumour necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein-1 increased in donors with prediabetes compared to normal donors. GSIS response was significantly decreased in pre-diabetic islets compared to normal islets. Donors with prediabetes also had decreased expression of CD163+ cells but not CD68+ cells. CONCLUSIONS Based on our findings, inflammation and islet dysfunction may be more significant than originally thought in people with prediabetes. Rather than being in a normal state before diabetes occurs, it appears that subjects are already in an early diabetic condition resembling more closely T2D.
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Affiliation(s)
- Jessica R Weaver
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Justin J Odanga
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Erick K Breathwaite
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Michelle L Treadwell
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Angela C Murchinson
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Gary Walters
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Danette P Fuentes
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
| | - Jung Bok Lee
- Institute of Regenerative Medicine, LifeNet Health, Virginia Beach, Virginia, USA
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Li X, Sun F, Lu J, Zhang J, Wang J, Zhu H, Gu M, Ma J. Osteoclasts May Affect Glucose Uptake-Related Insulin Resistance by Secreting Resistin. Diabetes Metab Syndr Obes 2021; 14:3461-3470. [PMID: 34366677 PMCID: PMC8336992 DOI: 10.2147/dmso.s316964] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/06/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVES Bone may play a role in the modulation of insulin sensitivity. Insulin resistance can be caused by increased resistin. However, whether osteoclasts affect the insulin resistance via resistin remains unclear. In the present study, we show the expression of resistin in osteoclasts and the possible underlying role of resistin on glucose uptake-related insulin resistance in vitro. METHODS Conditioned mediums (CM) were collected from Raw264.7 cells treated without (CCM) or with RANKL (CM3, treated with RANKL for 3 days; CM5, treated with RANKL for 5 days) and transfected with control or resistin siRNA (CMsiRNA). The osteoclast formation was examined by tartrate resistant acid phosphatase (TRAP) staining. C2C12 myoblasts were cultured with the CM or CMsiRNA. Glucose uptake was evaluated by 2-NBDG fluorescence intensity. Resistin expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay. Statistical analysis was performed by an independent two sample t-test or one-way ANOVA. RESULTS The 2-NBDG fluorescence intensity was higher in C2C12 cells treated with CCM compared to those that received CM3 and CM5 (p < 0.05). Resistin mRNA and protein expressions were both increased in RAW264.7 cells treated with RANKL for 3 days and 5 days compared with those cells without RANKL administration. The 2-NBDG fluorescence intensities in C2C12 cells treated with CMsiRNA and CM5+Anti-resistin antibody were significantly higher than those cultured with CM5 (p < 0.05). CONCLUSION Osteoclasts may promote glucose uptake-related insulin resistance by secreting resistin.
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Affiliation(s)
- Xiangqi Li
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Fei Sun
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Jiancan Lu
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Jichen Zhang
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Jingnan Wang
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Hongling Zhu
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Mingjun Gu
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
| | - Junhua Ma
- Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China
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Perpétuo L, Voisin PM, Amado F, Hirtz C, Vitorino R. Ghrelin and adipokines: An overview of their physiological role, antimicrobial activity and impact on cardiovascular conditions. VITAMINS AND HORMONES 2021; 115:477-509. [PMID: 33706959 DOI: 10.1016/bs.vh.2020.12.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The human body has many different hormones that interact with each other and with other factors such as proteins, cell receptors and metabolites. There is still a limited understanding of some of the underlying biological mechanisms of some hormones. In the past decades, science and technology have made major advancements in regard to innovation and knowledge in fields such as medicine. However, some conditions are complex and have many variables that their full picture is still unclear, even though some of these conditions have an alarming rate of incidence and serious health consequences. Conditions such as type 2 diabetes, obesity, nonalcoholic liver disease (NAFLD), cancer in its different forms and even mental conditions, such as Alzheimer's disease, are some of the most common diseases in the 21st century. These conditions are relevant not only because of their high incidence on the general population, but also because of their severity. In this chapter, we present an overview of cardiovascular (CV) diseases. According to the World Health Organization (WHO), cardiovascular diseases, such as coronary artery disease (CAD), heart attack, cardiomyopathy and heart failure (among others), are the number one cause of death worldwide. In 2016, it was estimated that 17.9 million people died from CV diseases, representing more than 30% of all global deaths. Approximately 95% of people who died from CV diseases were so-called "premature deaths" because were referenced to individuals under the age of 70 years old. In this chapter we described some of the hormones that may have an impact on CV diseases, including ghrelin, a peptide that is mostly produced in the stomach, known to induce hunger. Ghrelin is linked to an increase in body fat, i.e., adipose tissue in animals. For this reason, we also included the adipokines leptin, adiponectin and resistin. The main objectives of this chapter are to present the state of the art knowledge concerning the mechanisms of each hormone relevant to CV diseases; to compile data and results that further elucidate the relevance of these peptides for several physiological events, conditions and diseases; and to discuss the metabolic impact of each hormone. We established connections between multiple peptides and the underlying condition/disease with tools such as STRING, referring to research using databases, such as UniProt, DisGeNET and Proteomics DB. Fig. 1 shows a network that summarizes the information presented in this chapter, which serves as a visual representation.
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Affiliation(s)
- Luís Perpétuo
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | | | - Francisco Amado
- LAQV-REQUIMTE, Departamento de Química, Universidade de Aveiro, Aveiro, Portugal
| | - Christophe Hirtz
- IRMB, Univ Montpellier, INSERM, CHU Montpellier, CNRS, Montpellier, France
| | - Rui Vitorino
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; UnIC, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; LAQV-REQUIMTE, Departamento de Química, Universidade de Aveiro, Aveiro, Portugal.
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Farahani H, Mahmoudi T, Asadi A, Nobakht H, Dabiri R, Hamta A. Insulin Resistance and Colorectal Cancer Risk: the Role of Elevated Plasma Resistin Levels. J Gastrointest Cancer 2021; 51:478-483. [PMID: 31168777 DOI: 10.1007/s12029-019-00260-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Given the important role of resistin in insulin resistance (IR) and obesity, as well as the associations between both IR and obesity and increased risk of colorectal cancer (CRC), we investigated whether plasma resistin levels were associated with CRC risk. Furthermore, the possible correlations between resistin and insulin, IR, and obesity in patients with CRC and controls were explored. METHODS This study was conducted as a case-control study and 170 subjects, including 88 controls and 82 cases with CRC, were enrolled and their plasma levels of glucoe, insulin, and resistin were measured using glucose oxidase or ELISA methods. Moreover, IR was calculated according to HOMA-IR index. RESULTS The cases with CRC had a higher HOMA-IR than the controls (1.8 ± 0.4 versus 1.4 ± 0.3, P < 0.001). Additionally, after the stratification of the cases with CRC by tumor site, higher levels of resistin and insulin, and a higher HOMA-IR in the cases with rectal cancer than in the controls were observed (resistin 5.9 ± 1.2 versus 5.4 ± 1.3, P = 0.043; insulin 5.9 ± 1.2 versus 5.4 ± 1.3, P = 0.039; HOMA- IR 1.9 ± 0.4 versus 1.3 ± 0.3, P < 0.001). Furthermore, resistin was positively correlated with insulin in the controls (r = 0.737, P < 0.001), the cases with CRC (r = 0.881, P < 0.001), the cases with colon cancer (r = 0.811, P < 0.001), and the cases with rectal cancer (r = 0.990, P < 0.001). All these differences remained significant after adjustment for confounding factors. CONCLUSIONS The findings of the present study reinforce the hypothesis that higher plasma levels of resistin in connection with insulin resistance play a role in susceptibility to colorectal, notably rectal, cancer. Nevertheless, further studies with bigger sample sizes are required to validate these findings.
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Affiliation(s)
- Hamid Farahani
- Department of Physiology, School of Medicine, Qom University of Medical Sciences, Alqadir Boulevard, 3736175513, Qom, Iran.
| | - Touraj Mahmoudi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Hossein Nobakht
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Reza Dabiri
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Amir Hamta
- Department of Social Medicine, School of Medicine, Qom University of Medical Sciences, Qom, Iran
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11
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Recinella L, Orlando G, Ferrante C, Chiavaroli A, Brunetti L, Leone S. Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases. Front Physiol 2020; 11:578966. [PMID: 33192583 PMCID: PMC7662468 DOI: 10.3389/fphys.2020.578966] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/14/2020] [Indexed: 12/11/2022] Open
Abstract
Besides its role as an energy storage organ, adipose tissue can be viewed as a dynamic and complex endocrine organ, which produces and secretes several adipokines, including hormones, cytokines, extracellular matrix (ECM) proteins, and growth and vasoactive factors. A wide body of evidence showed that adipokines play a critical role in various biological and physiological functions, among which feeding modulation, inflammatory and immune function, glucose and lipid metabolism, and blood pressure control. The aim of this review is to summarize the effects of several adipokines, including leptin, diponectin, resistin, chemerin, lipocalin-2 (LCN2), vaspin, omentin, follistatin-like 1 (FSTL1), secreted protein acidic and rich in cysteine (SPARC), secreted frizzled-related protein 5 (SFRP5), C1q/TNF-related proteins (CTRPs), family with sequence similarity to 19 member A5 (FAM19A5), wingless-type inducible signaling pathway protein-1 (WISP1), progranulin (PGRN), nesfatin-1 (nesfatin), visfatin/PBEF/NAMPT, apelin, retinol binding protein 4 (RPB4), and plasminogen activator inhibitor-1 (PAI-1) in the regulation of insulin resistance and vascular function, as well as many aspects of inflammation and immunity and their potential role in managing obesity-associated diseases, including metabolic, osteoarticular, and cardiovascular diseases.
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Affiliation(s)
| | | | | | | | - Luigi Brunetti
- Department of Pharmacy, Gabriele d’Annunzio University, Chieti, Italy
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12
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Su KZ, Li YR, Zhang D, Yuan JH, Zhang CS, Liu Y, Song LM, Lin Q, Li MW, Dong J. Relation of Circulating Resistin to Insulin Resistance in Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis. Front Physiol 2019; 10:1399. [PMID: 31803062 PMCID: PMC6877503 DOI: 10.3389/fphys.2019.01399] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/30/2019] [Indexed: 12/20/2022] Open
Abstract
Background: Resistin, a cysteine-rich polypeptide encoded by the RETN gene, which plays an important role in many mechanisms in rodent studies, including lipid metabolism, inflammation and insulin resistance. Nevertheless, the relationship between resistin and insulin resistance in humans is under debate. The present study was designed to clarify the correlation between resistin and insulin resistance. Methods: A systematic literature search was performed using PubMed, Embase and Cochrane Library until March 3, 2019 with the keywords "resistin" and "insulin resistance." Funnel plots and Egger's test were used to detect publication bias. A random-effects model was used to calculate the pooled effect size. Subgroup analysis and meta regression was performed to identify the sources of heterogeneity. Results: Fifteen studies were included in our systematic review. Among them, 10 studies with Pearson coefficients were used for meta-analysis. We found resistin levels were weakly correlated with insulin resistance in those with T2DM and obesity (r = 0.21, 95% CI: 0.06-0.35, I 2 = 59.7%, P = 0.003). Nevertheless, subgroup analysis suggested that circulating resistin levels were significantly positively correlated with insulin resistance in individuals with hyperresistinemia (≥14.8 ng/ml) (r = 0.52, 95% CI: 0.35-0.68, I 2 = 0.0%, P = 0.513). And there was no relationship between circulating resistin and insulin resistance in those with normal circulating resistin levels (<14.8 ng/ml) (r = 0.08, 95% CI: -0.01-0.18, I 2 = 0.0%, P = 0.455). Publication bias was insignificant (Egger's test P = 0.592). Conclusion: In T2DM and obese individuals, resistin levels were positively correlated with insulin resistance in those with hyperresistinemia, but not in those with normal circulating resistin levels.
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Affiliation(s)
- Kai-zhen Su
- Clinical Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Yan-run Li
- Clinical Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Di Zhang
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Jun-hua Yuan
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Cai-shun Zhang
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Yuan Liu
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Li-min Song
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Qian Lin
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Man-wen Li
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
| | - Jing Dong
- Special Medicine Department, Medical College, Qingdao University, Qingdao, China
- Physiology Department, Medical College, Qingdao University, Qingdao, China
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13
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Lelis DDF, Freitas DFD, Machado AS, Crespo TS, Santos SHS. Angiotensin-(1-7), Adipokines and Inflammation. Metabolism 2019; 95:36-45. [PMID: 30905634 DOI: 10.1016/j.metabol.2019.03.006] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 03/11/2019] [Accepted: 03/20/2019] [Indexed: 12/12/2022]
Abstract
Nowadays the adipose tissue is recognized as one of the most critical endocrine organs releasing many adipokines that regulate metabolism, inflammation and body homeostasis. There are several described adipokines, including the renin-angiotensin system (RAS) components that are especially activated in some diseases with increased production of angiotensin II and several pro-inflammatory hormones. On the other hand, RAS also expresses angiotensin-(1-7), which is now recognized as the main peptide on counteracting Ang II effects. New studies have shown that increased activation of ACE2/Ang-(1-7)/MasR arm can revert and prevent local and systemic dysfunctions improving lipid profile and insulin resistance by modulating insulin actions, and reducing inflammation. In this context, the present review shows the interaction and relevance of Ang-(1-7) effects on regulating adipokines, and as one adipokine itself, modulating body homeostasis, with emphasis on its anti-inflammatory properties, especially in the context of metabolic disorders with focus on obesity and type 2 diabetes mellitus pandemic.
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Affiliation(s)
- Deborah de Farias Lelis
- Laboratory of Health Sciences, Post Graduate Program in Health Sciences, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Minas Gerais, Brazil
| | - Daniela Fernanda de Freitas
- Laboratory of Health Sciences, Post Graduate Program in Health Sciences, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Minas Gerais, Brazil
| | - Amanda Souto Machado
- Laboratory of Health Sciences, Post Graduate Program in Health Sciences, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Minas Gerais, Brazil
| | - Thaísa Soares Crespo
- Laboratory of Health Sciences, Post Graduate Program in Health Sciences, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Minas Gerais, Brazil
| | - Sérgio Henrique Sousa Santos
- Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil; Laboratory of Health Sciences, Post Graduate Program in Health Sciences, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Minas Gerais, Brazil.
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14
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Hu SM, Chen MS, Tan HZ. Maternal serum level of resistin is associated with risk for gestational diabetes mellitus: A meta-analysis. World J Clin Cases 2019; 7:585-599. [PMID: 30863758 PMCID: PMC6406206 DOI: 10.12998/wjcc.v7.i5.585] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/02/2019] [Accepted: 02/18/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Resistin is most likely involved in the pathogenesis of gestational diabetes mellitus (GDM), but the existing findings are inconsistent.
AIM To review the literature investigating the associations of the risk of GDM with serum level of resistin.
METHODS A systematic literature search was performed using MEDLINE, EMBASE, and Web of Science (all databases). This meta-analysis included eligible studies that: (1) investigated the relationship between the risk of GDM and serum resistin; (2) included GDM cases and controls without GDM; (3) diagnosed GDM according to the oral glucose-tolerance test; (4) were performed in humans; (5) were published as full text articles in English; and (6) provided data with median and quartile range, median and minimum and maximum values, or mean and standard deviation. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to estimate the association between the risk of GDM and serum resistin. To analyze the potential influences of need for insulin in GDM patients and gestational age at blood sampling, we performed a subgroup analysis. Meta-regression with restricted maximum likelihood estimation was performed to assess the potentially important covariate exerting substantial impact on between-study heterogeneity.
RESULTS The meta-analysis for the association between serum resistin level and GDM risk included 18 studies (22 comparisons) with 1041 cases and 1292 controls. The total results showed that the risk of GDM was associated with higher serum resistin level (SMD = 0.250, 95%CI: 0.116, 0.384). The “after 28 wk” subgroup, “no need for insulin” subgroup, and “need for insulin” subgroup indicated that higher serum resistin level was related to GDM risk (“after 28 wk” subgroup: SMD = 0.394, 95%CI: 0.108, 0.680; “no need for insulin” subgroup: SMD = 0.177, 95%CI: 0.018, 0.336; “need for insulin” subgroup: SMD = 0.403, 95%CI: 0.119, 0.687). The “before 14 wk” subgroup, “14-28 wk” subgroup, and “no information of need for insulin” subgroup showed a nonsignificant association between serum resistin level and GDM risk (“before 14 wk” subgroup: SMD = 0.087, 95%CI: -0.055, 0.230; “14-28 wk” subgroup: SMD = 0.217, 95%CI: -0.003, 0.436; “no information of need for insulin” subgroup: SMD = 0.356, 95%CI: -0.143, 0.855). The postpartum subgroup included only one study and showed that higher serum resistin level was related to GDM risk (SMD = 0.571, 95%CI: 0.054, 1.087) The meta-regression revealed that no need for insulin in GDM patients, age distribution similar between cases and controls, and ELISA all had a significant impact on between-study heterogeneity.
CONCLUSION This meta-analysis supports that the maternal serum resistin level is associated with GDM risk.
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Affiliation(s)
- Shi-Min Hu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
| | - Meng-Shi Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
| | - Hong-Zhuan Tan
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
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15
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Saeedi Borujeni MJ, Esfandiary E, Taheripak G, Codoñer-Franch P, Alonso-Iglesias E, Mirzaei H. Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome. J Cell Biochem 2018; 119:1257-1272. [PMID: 28688216 DOI: 10.1002/jcb.26271] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 07/07/2017] [Indexed: 12/16/2022]
Abstract
Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM.
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Affiliation(s)
- Mohammad Javad Saeedi Borujeni
- Department of Anatomical SCIENCES and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ebrahim Esfandiary
- Department of Anatomical SCIENCES and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Taheripak
- Faculty of Medicine, Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran
| | - Pilar Codoñer-Franch
- Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain
| | | | - Hamed Mirzaei
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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16
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Siddiqui K, George TP. Resistin role in development of gestational diabetes mellitus. Biomark Med 2017; 11:579-586. [PMID: 28685604 DOI: 10.2217/bmm-2017-0013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Diabetes is estimated to be one of the major causes of deaths in most countries due to its high prevalence rate, which was 8.8% in 2015. Hyperglycemia detected during pregnancy is known as gestational diabetes mellitus and it increases the potential risk of development of Type 2 diabetes in mothers with its varying prevalence rate of 1-14% in different populations. It also leads to the higher risk of developing abnormal glucose tolerance and obesity in their child at an early age. Recent studies show that potential mediators of insulin resistance such as adipokines - adiponectin, leptin and resistin are important for glucose and lipid metabolism. Adipokines are directly involved in the regulation of insulin secretion and insulin sensitivity in the liver, muscle and adipose tissue. It is also involved in inflammation, adipose tissue accumulation, adverse fat distribution and subsequently affects glucose metabolism. This review highlights the role of resistin (an adipokine) in the development of gestational diabetes mellitus.
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Affiliation(s)
- Khalid Siddiqui
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Teena P George
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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17
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Oh YK, Ha YR, Yi KW, Park HT, Shin JH, Kim T, Hur JY. Increased expression of resistin in ectopic endometrial tissue of women with endometriosis. Am J Reprod Immunol 2017; 78. [PMID: 28681517 DOI: 10.1111/aji.12726] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 06/01/2017] [Indexed: 11/26/2022] Open
Abstract
PROBLEM Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear. METHOD OF STUDY Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays. RESULTS Resistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosis than in normal eutopic endometrial tissue. CONCLUSION Our results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation.
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Affiliation(s)
- Yoon Kyung Oh
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Young Ran Ha
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Kyong Wook Yi
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Hyun Tae Park
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Jung-Ho Shin
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Tak Kim
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Jun-Young Hur
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
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18
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Wen F, Yang Y, Sun C, Fang H, Nie L, Li L, Liu Y, Yang Z. RESISTIN INHIBITS GLUCOSE-STIMULATED INSULIN SECRETION THROUGH MIR-494 BY TARGET ON STXBP5. ACTA ENDOCRINOLOGICA-BUCHAREST 2017; 13:32-39. [PMID: 31149145 DOI: 10.4183/aeb.2017.32] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Aims Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. Methods Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. Results Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3'UTR. Conclusion miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.
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Affiliation(s)
- F Wen
- Henan University of Science and Technology, College of Animal Science and Technology, Luoyang, Henan, PR China.,Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
| | - Y Yang
- Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
| | - C Sun
- Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
| | - H Fang
- Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
| | - L Nie
- Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
| | - L Li
- Henan University of Science and Technology, College of Animal Science and Technology, Luoyang, Henan, PR China
| | - Y Liu
- Henan University of Science and Technology, College of Animal Science and Technology, Luoyang, Henan, PR China
| | - Z Yang
- Huazhong Agricultural University, College of Life Science and Technology, Breeding and Reproduction of Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, Hubei, PR China
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19
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Sassek M, Pruszynska-Oszmalek E, Kołodziejski PA, Szczepankiewicz D, Kaczmarek P, Wieloch M, Kurto K, Nogowski L, Nowak KW, Strowski MZ, Mackowiak P. Resistin is produced by rat pancreatic islets and regulates insulin and glucagon in vitro secretion. Islets 2016; 8:177-185. [PMID: 27797297 PMCID: PMC5161143 DOI: 10.1080/19382014.2016.1251538] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Resistin participates in the regulation of energy homeostasis, insulin resistance, and inflammation. The potential expression in pancreas, and modulation of the endocrine pancreas secretion by resistin is not well characterized, therefore, we examined it on several levels. We examined the localization of resistin in rat pancreatic islets by immunohistochemistry and immunofluorescence, and the potential presence of resistin mRNA by RT-PCR and protein by Western Blot in these structures. In addition, we studied the regulation of insulin and glucagon secretion by resistin in pancreatic INS-1E β- and InR-G9 α-cell lines as well as isolated rat pancreatic islets. We identified resistin immunoreactivity in the periphery of rat pancreatic islets and confirmed the expression of resistin at mRNA and protein level. Obtained data indicated that resistin is co-localized with glucagon in pancreatic α-cells. In addition, we found that in vitro resistin decreased insulin secretion from INS-1E cells and pancreatic islets at normal (6 mM) and high (24 mM) glucose concentrations, and also decreased glucagon secretion from G9 cells and pancreatic islets at 1 mM, whereas a stimulation of glucagon secretion was observed at 6 mM glucose. Our results suggest that resistin can modulate the secretion of insulin and glucagon from clonal β or α cells, and from pancreatic islets.
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Affiliation(s)
- Maciej Sassek
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
- CONTACT Maciej Sassek Department of Animal Physiology and Biochemistry, University of Live Science, Wolynska str. 35, Poznan 60637, Poland
| | - Ewa Pruszynska-Oszmalek
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Paweł A. Kołodziejski
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Dawid Szczepankiewicz
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Przemyslaw Kaczmarek
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Marianna Wieloch
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
- Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland
| | - Katarzyna Kurto
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Leszek Nogowski
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Krzysztof W. Nowak
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
| | - Mathias Z. Strowski
- Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland
- Department of Hepatology and Gastroenterology and the Interdisciplinary Center of Metabolism, Endocrinology, Diabetes and Metabolism, Charité-University Medicine, Berlin, Germany
- Department of Internal Medicine - Gastroenterology, Park-Klinik Weissensee, Berlin, Germany
| | - Pawel Mackowiak
- Department of Animal Physiology and Biochemistry, University of Live Sciences, Poznan, Poland
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20
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Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest 2016; 39:607-15. [PMID: 26662574 DOI: 10.1007/s40618-015-0408-2] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 10/24/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE This review aimed to discuss the conflicting findings from resistin research in rodents and humans as well as recent advances in our understanding of resistin's role in obesity and insulin resistance. METHODS A comprehensive review and synthesis of resistin's role in obesity and insulin resistance as well as conflicting findings from resistin research in rodents and humans. RESULTS In rodents, resistin is increased in high-fat/high-carbohydrate-fed, obese states characterized by impaired glucose uptake and insulin sensitivity. Resistin plays a causative role in the development of insulin resistance in rodents via 5' AMP-activated protein kinase (AMPK)-dependent and AMPK-independent suppressor of cytokine signaling-3 (SOCS-3) signaling. In contrast to rodents, human resistin is primarily secreted by peripheral-blood mononuclear cells (PBMCs) as opposed to white adipocytes. Circulating resistin levels have been positively associated with central/visceral obesity (but not BMI) as well as insulin resistance, while other studies show no such association. Human resistin has a role in pro-inflammatory processes that have been conclusively associated with obesity and insulin resistance. PBMCs, as well as vascular cells, have been identified as the primary targets of resistin's pro-inflammatory activity via nuclear factor-κB (NF-κB, p50/p65) and other signaling pathways. CONCLUSION Mounting evidence reveals a continuing disconnect between resistin's role in rodents and humans due to significant differences between these two species with respect to resistin's gene and protein structure, differential gene regulation, tissue-specific distribution, and insulin resistance induction as well as a paucity of evidence regarding the resistin receptor and downstream signaling mechanisms of action.
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Affiliation(s)
- X Huang
- Department of Radiology, College of Basic Medicine, Chongqing Medical University, Chongqing, China
- Department of Internal Medicine, Hechuan Hospital of First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Z Yang
- Department of Internal Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Kibar YI, Albayrak F, Arabul M, Dursun H, Albayrak Y, Ozturk Y. Resistin: New serum marker for predicting severity of acute pancreatitis. J Int Med Res 2016; 44:328-37. [PMID: 26857860 PMCID: PMC5580057 DOI: 10.1177/0300060515605428] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 08/19/2015] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To assess the effectiveness of resistin in predicting the severity of acute pancreatitis. METHODS Patients with acute pancreatitis who presented at the Gastroenterology Clinic, Erzurum Education and Research Hospital, Turkey were enrolled in this prospective study. White blood cell (WBC), C-reactive protein (CRP) and resistin levels were measured on admission and at 24 h, day 3 and day 7 following admission, along with other blood parameters. Patients were divided into two groups: mild acute pancreatitis and moderate/severe acute pancreatitis. RESULTS Of 59 patients with acute pancreatitis (mild, n = 37; moderate/severe, n = 22), significant between-group differences were found in terms of resistin and CRP levels. Receiver operating curve analysis showed that resistin levels were better for predicting severe cases of acute pancreatitis than CRP or WBC levels on day 3 (area under the curve [AUC], 0.88 versus 0.81 and 0.63, respectively). Resistin levels on day 3 were better than CRP levels for predicting necrosis development (AUC, 0.70 versus 0.69, respectively). CONCLUSIONS Resistin may represent a new, effective indicator to predict the severity of acute pancreatitis and presence of necrosis in patients with acute pancreatitis.
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Affiliation(s)
- Yunus I Kibar
- Department of Internal Medicine, Education and Research Hospital, Erzurum, Turkey
| | - Fatih Albayrak
- Department of Internal Medicine, Section of Gastroenterology, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Mahmut Arabul
- Department of Internal Medicine, Education and Research Hospital, Erzurum, Turkey
| | - Hakan Dursun
- Department of Internal Medicine, Section of Gastroenterology, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Yavuz Albayrak
- Department of Surgery, Education and Research Hospital, Erzurum, Turkey
| | - Yasin Ozturk
- Department of Internal Medicine, Education and Research Hospital, Erzurum, Turkey
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22
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Rak-Mardyła A, Drwal E. In vitro interaction between resistin and peroxisome proliferator-activated receptor γ in porcine ovarian follicles. Reprod Fertil Dev 2016; 28:357-68. [DOI: 10.1071/rd14053] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 06/13/2014] [Indexed: 11/23/2022] Open
Abstract
In the present study, using real-time polymerase chain reaction and immunoblotting methods, we quantified the expression of peroxisome proliferator-activated receptor (PPAR) γ, PPARα and PPARβ in different sized ovarian follicles (small (SF), medium (MF) and large (LF) follicles) in prepubertal and adult pigs. In prepubertal pigs, PPARγ and PPARα expression was highest in LF; however, PPARβ expression did not differ among SF, MF and LF. In mature pigs, only protein expression of PPARγ and PPARα increased during ovarian follicle development. Following identification of very high levels of PPARγ expression in LF in prepubertal and adult pigs, using in vitro culture of ovarian follicles, we determined the effect of resistin at 0.1, 1 and 10 ng mL–1 on PPARγ mRNA and protein expression and the effect of rosiglitazone at 25 and 50 µM (a PPARγ agonist) on resistin mRNA and protein expression. Resistin increased PPARγ expression in ovarian follicles in both prepubertal and adult pigs, whereas rosiglitazone had an inhibitory effect on resistin expression. The role of PPARγ in regulating the effects of resistin on ovarian steroidogenesis was investigated using GW9662 (a PPARγ antagonist at dose of 1 μM). In these studies, GW9662 reversed the effect of resistin on steroid hormone secretion. The data suggest that there is local cooperation between resistin and PPARγ expression in the porcine ovary. Resistin significantly increased the expression of PPARγ, whereas PPARγ decreased resistin expression; thus, PPARγ is a new key regulator of resistin expression and function.
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Christiansen M, Hedley PL, Placing S, Wøjdemann KR, Carlsen AL, Jørgensen JM, Gjerris AC, Shalmi AC, Rode L, Sundberg K, Tabor A. Maternal Serum Resistin Is Reduced in First Trimester Preeclampsia Pregnancies and Is a Marker of Clinical Severity. Hypertens Pregnancy 2015; 34:422-433. [PMID: 26636480 DOI: 10.3109/10641955.2014.913615] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To examine whether resistin levels in first trimester maternal serum are associated with insulin resistance or preeclampsia (PE). METHODS A case-control study of maternal serum resistin concentration conducted using 285 normal pregnancies and 123 PE pregnancies matched for gestational age, parity and maternal age. Samples were taken in gestational weeks 10+0-13+6. RESULTS There was a negative correlation between resistin and clinical severity of PE, but no correlation with IS, TNF-α, body mass index, birth weight and pregnancy length. CONCLUSIONS Resistin is reduced in first trimester of PE pregnancies, particularly in severe PE. Inflammation and IS cannot explain this phenomenon.
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Affiliation(s)
- Michael Christiansen
- a Department of Clinical Biochemistry , Statens Serum Institut , Copenhagen , Denmark
| | - Paula L Hedley
- a Department of Clinical Biochemistry , Statens Serum Institut , Copenhagen , Denmark .,b Department of Biomedical Sciences , Stellenbosch University , Cape Town , South Africa
| | - Sophie Placing
- a Department of Clinical Biochemistry , Statens Serum Institut , Copenhagen , Denmark
| | - Karen R Wøjdemann
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark .,d Department of Obstetrics and Gynecology , Roskilde Hospital , Roskilde , Denmark
| | - Anting L Carlsen
- a Department of Clinical Biochemistry , Statens Serum Institut , Copenhagen , Denmark
| | - Jennifer M Jørgensen
- a Department of Clinical Biochemistry , Statens Serum Institut , Copenhagen , Denmark
| | - Anne-Cathrine Gjerris
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark .,e Department of Obstetrics and Gynecology , Hillerød Hospital , Hillerød , Denmark
| | - Anne-Cathrine Shalmi
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark .,e Department of Obstetrics and Gynecology , Hillerød Hospital , Hillerød , Denmark
| | - Line Rode
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark
| | - Karin Sundberg
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark
| | - Ann Tabor
- c Department of Fetal Medicine , Rigshospitalet , Copenhagen , Denmark
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Rak A, Drwal E, Karpeta A, Gregoraszczuk EŁ. Regulatory Role of Gonadotropins and Local Factors Produced by Ovarian Follicles on In Vitro Resistin Expression and Action on Porcine Follicular Steroidogenesis1. Biol Reprod 2015; 92:142. [DOI: 10.1095/biolreprod.115.128611] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 04/23/2015] [Indexed: 12/22/2022] Open
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XUE LENING, WANG XIAOYONG, TAN YONG, LIN MIN, ZHANG WEI, XU KEQUN. Significance of resistin expression in acute pancreatitis. Exp Ther Med 2015; 9:1438-1442. [PMID: 25780448 PMCID: PMC4353746 DOI: 10.3892/etm.2015.2270] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 10/28/2014] [Indexed: 01/04/2023] Open
Abstract
The aim of the present study was to detect the expression of resistin in rats with acute pancreatitis (AP) and investigate its significance in the pathogenesis of AP. In total, 40 Sprague-Dawley rats were randomly divided into four groups (n=10), including the normal control, sham-operated, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) groups. Following the establishment of animal models, the levels of serum resistin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β were measured using ELISA. Resistin expression in the pancreatic tissues was detected using an immunohistochemical method. In addition, the mRNA expression of resistin in the pancreatic tissues was analyzed with quantitative polymerase chain reaction. The levels of serum amylase, serum resistin, TNF-α, IL-1β and CRP were all significantly higher in the AEP and ANP groups when compared with the control and sham-operated groups (P<0.01), as were the pancreas/body weight ratios and pathological scores of the pancreas. These increases were more significant in the ANP group than in the AEP group (P<0.05). The mRNA expression levels of resistin in the pancreatic tissues were markedly higher in the AEP and ANP groups when compared with the control and sham-operated groups (P<0.01), particularly in the pancreatic tissues of the ANP group, which exhibited notably higher levels compared with the AEP group. The serum resistin level was found to positively correlate with the serum levels of CRP, TNF-α and IL-1β, and the pathological scores of the pancreatic tissues. In conclusion, the results indicated that resistin may be associated with the occurrence and development of AP; thus, the protein may be a valuable indicator for assessing the severity of AP.
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Affiliation(s)
| | | | | | - MIN LIN
- Department of Gastroenterology, Changzhou Second Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China
| | - WEI ZHANG
- Department of Gastroenterology, Changzhou Second Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China
| | - KE-QUN XU
- Department of Gastroenterology, Changzhou Second Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China
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Al Hannan F, Culligan KG. Human resistin and the RELM of Inflammation in diabesity. Diabetol Metab Syndr 2015; 7:54. [PMID: 26097512 PMCID: PMC4474570 DOI: 10.1186/s13098-015-0050-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 06/05/2015] [Indexed: 12/11/2022] Open
Abstract
The initial discovery of resistin and resistin-like molecules (RELMs) in rodents suggested a role for these adipocytokines in molecular linkage of obesity, Type 2 Diabetes mellitus and metabolic syndrome. Since then, it became apparent that the story of resistin and RELMs was very much of mice and men. The putative role of this adipokine family evolved from that of a conveyor of insulin resistance in rodents to instigator of inflammatory processes in humans. Structural dissimilarity, variance in distribution profiles and a lack of corroborating evidence for functional similarities separate the biological functions of resistin in humans from that of rodents. Although present in gross visceral fat deposits in humans, resistin is a component of inflammation, being released from infiltrating white blood cells of the sub-clinical chronic low grade inflammatory response accompanying obesity, rather than from the adipocyte itself. This led researchers to further explore the functions of the resistin family of proteins in inflammatory-related conditions such as atherosclerosis, as well as in cancers such as endometrial and gastric cancers. Although elevated levels of resistin have been found in these conditions, whether it is causative or as a result of these conditions still remains to be determined.
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Affiliation(s)
- Fatima Al Hannan
- />Department of Biomedical Sciences, Royal College of Surgeons in Ireland – Bahrain, Building No. 2441, Road 2835, Busaiteen, Kingdom of Bahrain
| | - Kevin Gerard Culligan
- />Department of Biomedical Sciences, Royal College of Surgeons in Ireland – Bahrain, Building No. 2441, Road 2835, Busaiteen, Kingdom of Bahrain
- />Royal College of Surgeons in Ireland – Bahrain, PO Box 15503, Adliya, Kingdom of Bahrain
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Ogawa H, Damrongrungruang T, Hori S, Nouno K, Minagawa K, Sato M, Miyazaki H. Effect of periodontal treatment on adipokines in type 2 diabetes. World J Diabetes 2014; 5:924-931. [PMID: 25512798 PMCID: PMC4265882 DOI: 10.4239/wjd.v5.i6.924] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 09/29/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.
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Al-Maramhy H, Abdelrahman AI, Sawalhi S. Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: A case-controlled study. World J Gastroenterol 2014; 20:15351-15357. [PMID: 25386084 PMCID: PMC4223269 DOI: 10.3748/wjg.v20.i41.15351] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 02/16/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity.
METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age.
RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m2 (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity.
CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity.
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Reverchon M, Ramé C, Bertoldo M, Dupont J. Adipokines and the female reproductive tract. Int J Endocrinol 2014; 2014:232454. [PMID: 24695544 PMCID: PMC3948585 DOI: 10.1155/2014/232454] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Accepted: 12/27/2013] [Indexed: 12/15/2022] Open
Abstract
It is well known that adipose tissue can influence puberty, sexual maturation, and fertility in different species. Adipose tissue secretes molecules called adipokines which most likely have an endocrine effect on reproductive function. It has been revealed over the last few years that adipokines are functionally implicated at all levels of the reproductive axis including the gonad and hypothalamic-pituitary axis. Many studies have shown the presence and the role of the adipokines and their receptors in the female reproductive tract of different species. These adipokines regulate ovarian steroidogenesis, oocyte maturation, and embryo development. They are also present in the uterus and placenta where they could create a favorable environment for embryonic implantation and play a key role in maternal-fetal metabolism communication and gestation. Reproductive functions are strongly dependent on energy balance, and thereby metabolic abnormalities can lead to the development of some pathophysiologies such as polycystic ovary syndrome (PCOS). Adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS.
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Affiliation(s)
- Maxime Reverchon
- INRA, UMR85 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- CNRS, UMR6175 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- Université François Rabelais de Tours, 37041 Tours, France
- IFCE, 37380 Nouzilly, France
| | - Christelle Ramé
- INRA, UMR85 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- CNRS, UMR6175 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- Université François Rabelais de Tours, 37041 Tours, France
- IFCE, 37380 Nouzilly, France
| | - Michael Bertoldo
- INRA, UMR85 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- CNRS, UMR6175 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- Université François Rabelais de Tours, 37041 Tours, France
- IFCE, 37380 Nouzilly, France
| | - Joëlle Dupont
- INRA, UMR85 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- CNRS, UMR6175 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France
- Université François Rabelais de Tours, 37041 Tours, France
- IFCE, 37380 Nouzilly, France
- *Joëlle Dupont:
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Yang J, Kang J, Guan Y. The mechanisms linking adiposopathy to type 2 diabetes. Front Med 2013; 7:433-44. [PMID: 24085616 DOI: 10.1007/s11684-013-0288-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 07/19/2013] [Indexed: 02/06/2023]
Abstract
Obesity is defined as excessive accumulation of body fat in proportion to body size. When obesity occurs, the functions of adipose tissue may be deregulated, which is termed as adiposopathy. Adiposopathy is an independent risk factor for many diseases, including diabetes and cardiovascular diseases. In overweight or obese subjects with adiposopathy, hyperlipidemia exerts lipotoxicity in pancreatic islet and liver and induces pancreatic β cell dysfunction and liver insulin resistance, which are the decisive factors causing type 2 diabetes. Moreover, adipokines have been shown to play important roles in the regulation of glucose homeostasis. When adiposopathy occurs, abnormal changes in the serum adipokine profile correlate with the development and progression of pancreatic β cell dysfunction and insulin resistance in peripheral tissue. The current paper briefly discusses the latest findings regarding the effects of adiposopathy-related lipotoxicity and cytokine toxicity on the development of type 2 diabetes.
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Affiliation(s)
- Jichun Yang
- Department of Physiology and Pathophysiology, Peking University Diabetes Center, Peking University Health Science Center, Beijing, 100191, China
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Lu SY, He ZL, Sun TT, Li HJ, Chen PF. Rapid cloning and comparative sequence analysis of full-length cDNA of Rhesus monkey (Macaca mulatta) resistin. Am J Primatol 2013; 76:65-71. [PMID: 24038190 DOI: 10.1002/ajp.22194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Revised: 06/27/2013] [Accepted: 07/29/2013] [Indexed: 11/10/2022]
Abstract
Resistin protein is thought to link insulin resistance in murine models of obesity and type-2 diabetes, but the role of resistin in human studies of inflammatory metabolic disorders have generated conflicting data. Here, we describe the structure of the resistin gene using adipose tissue from non-human primates (NHPs), which have been used extensively to model a host of human diseases. Full-length cDNA from rhesus macaque resistin obtained by rapid amplification of cDNA ends (RACE) is comprised of 526 nucleotides covering an open-reading frame (ORF) that encodes a 108-amino-acid protein that is 92% homologous with the human counterpart but only 60% homologous with the murine counterpart. Using a modified polymerase chain reaction technique, we identified single nucleotide polymorphisms and a 78-bp deletion within resistin cDNA of nine rhesus macaques. Comparisons of the full-length cDNA sequence and an amplified 569-bp genomic DNA sequence revealed an error in published predictions arising from genomic studies about the gene's exon 3 region. Our data show, for the first time, the full-length macaque resistin cDNA sequence (GenBank: JF740676.1). These findings will illuminate future studies into the role of resistin in NHP models of inflammatory metabolic diseases.
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Affiliation(s)
- Shuai-Yao Lu
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China
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Pham MN, Kolb H, Mandrup-Poulsen T, Battelino T, Ludvigsson J, Pozzilli P, Roden M, Schloot NC. Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes: positive association with leptin and resistin and negative association with adiponectin. Diabetes Metab Res Rev 2013. [PMID: 23197433 DOI: 10.1002/dmrr.2378] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes. METHODS One hundred and eighteen patients with type 1 diabetes (20.3 ± 7.5 years) diagnosed <5 years underwent standardized mixed meal test (MMTT) for 2 h. Systemic concentrations of C-peptide, adiponectin, leptin and resistin obtained during MMTT were measured and compared between patient groups by multiple regression analysis. RESULTS Patients were divided by their adipokine levels in subgroups above or below the median level ('high versus low'). High adiponectin levels (>10.6 µg/mL) were associated with lower C-peptide compared to the low adiponectin subgroup (p < 0.03). Increased leptin or resistin concentrations associated positively with beta-cell function even after adjustment for metabolic confounders (p < 0.04). The described associations between adipokines and C-peptide concentrations persisted in Spearman correlation tests (p < 0.05). Serum adipokines fell during MMTT (p < 0.05). CONCLUSIONS Serum adipokine levels differentially correlate with beta-cell function in type 1 diabetes independent of BMI or metabolic control. Serum adipokines should be investigated as biomarkers of beta-cell function in prospective studies and intervention trials in type 1 diabetes.
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Affiliation(s)
- Minh Nguyet Pham
- Institute for Clinical Diabetology at German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany.
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Abstract
β-Cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes. Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors. In this review, we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of β-cells, focusing on those reported to have the most significant effects (leptin, adiponectin, tumour necrosis factor α, resistin, visfatin, dipeptidyl peptidase IV and apelin). It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to β-cell failure of changed concentrations of adipokines in the blood of obese pre-diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines, which act on the β-cell via a number of intersecting intracellular signalling pathways. We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on β-cells.
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Affiliation(s)
- Simon J Dunmore
- Diabetes and Metabolic Disease Research Group, Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
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Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism. Cytokine 2011; 56:157-66. [DOI: 10.1016/j.cyto.2011.06.023] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2010] [Revised: 06/22/2011] [Accepted: 06/27/2011] [Indexed: 12/26/2022]
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Yi KW, Shin JH, Park HT, Kim T, Kim SH, Hur JY. Resistin concentration is increased in the peritoneal fluid of women with endometriosis. Am J Reprod Immunol 2011; 64:318-23. [PMID: 20455877 DOI: 10.1111/j.1600-0897.2010.00840.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
PROBLEM The aim of this study was to investigate the concentration of resistin and adiponectin in the peritoneal fluid (PF) of patients with endometriosis. METHOD OF STUDY PF sampling was obtained from women with (n = 48) and without endometriosis (n = 36), and the anthropometric indices of the patients were measured. Resistin and adiponectin concentrations in the PF were determined using the enzyme-linked immunosorbent assay. RESULTS The mean concentration of PF resistin was significantly higher in women with endometriosis compared to the controls. PF resistin concentrations were not associated with any of the anthropometric indices. The PF adiponectin did not differ between the two groups, but showed a significant association with the weight, body mass index, and hip circumference. After adjusting for these factors, PF adiponectin expression was not associated with endometriosis. CONCLUSION The findings of this study suggest a potent role for resistin in endometriosis. Further studies are needed to elucidate the biological implications of resistin in endometriosis.
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Affiliation(s)
- Kyong Wook Yi
- Department of Obstetrics and Gynecology, Korea University, Seoul, Korea
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Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Ogge G, Yoon BH, Dong Z, Gonzalez JM, Gervasi MT, Hassan SS. Hyperresistinemia - a novel feature in systemic infection during human pregnancy. Am J Reprod Immunol 2010; 63:358-69. [PMID: 20178460 PMCID: PMC3426318 DOI: 10.1111/j.1600-0897.2010.00809.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
PROBLEM Resistin, originally described as an adipokine, has emerged as a potent pro-inflammatory protein associated with both acute and chronic inflammation. Moreover, resistin has been proposed as a powerful marker of sepsis severity, as well as a predictor of survival of critically ill non-pregnant patients. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma resistin concentrations. METHODS OF STUDY This cross-sectional study included the following groups: (i) normal pregnant women (n = 85) and (ii) pregnant women with pyelonephritis (n = 40). Maternal plasma resistin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. RESULTS (i) The median maternal plasma resistin concentration was higher in patients with pyelonephritis than in those with a normal pregnancy (P < 0.001); (ii) among patients with pyelonephritis, the median maternal resistin concentration did not differ significantly between those with and without a positive blood culture (P = 0.3); (iii) among patients with pyelonephritis who were diagnosed with systemic inflammatory response syndrome (SIRS), those who fulfilled > or =3 criteria for SIRS had a significantly higher median maternal plasma resistin concentration than those who met only two criteria; and (iv) maternal WBC count positively correlated with circulating resistin concentration (r = 0.47, P = 0.02). CONCLUSION Hyperresistinemia is a feature of acute pyelonephritis during pregnancy. The results of this study support the role of resistin as an acute-phase protein in the presence of bacterial infection during pregnancy.
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Affiliation(s)
- Shali Mazaki-Tovi
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Edi Vaisbuch
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Roberto Romero
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI
| | - Juan Pedro Kusanovic
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Tinnakorn Chaiworapongsa
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Sun Kwon Kim
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Giovanna Ogge
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Bo H. Yoon
- Department of Obstetrics and Gynecology, Seoul National University, Seoul, South Korea
| | - Zhong Dong
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Juan M. Gonzalez
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Maria Teresa Gervasi
- Department of Obstetrics and Gynecology, Azienda Ospedaliera of Padova, Padova, Italy
| | - Sonia S. Hassan
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
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Wang C, Guan Y, Yang J. Cytokines in the Progression of Pancreatic β-Cell Dysfunction. Int J Endocrinol 2010; 2010:515136. [PMID: 21113299 PMCID: PMC2989452 DOI: 10.1155/2010/515136] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2010] [Revised: 08/05/2010] [Accepted: 10/07/2010] [Indexed: 12/29/2022] Open
Abstract
The dysfunction of pancreatic β-cell and the reduction in β-cell mass are the decisive events in the progression of type 2 diabetes. There is increasing evidence that cytokines play important roles in the procedure of β-cell failure. Cytokines, such as IL-1β, IFN-γ, TNF-α, leptin, resistin, adiponectin, and visfatin, have been shown to diversely regulate pancreatic β-cell function. Recently, islet-derived cytokine PANcreatic DERived factor (PANDER or FAM3B) has also been demonstrated to be a regulator of islet β-cell function. The change in cytokine profile in islet and plasma is associated with pancreatic β-cell dysfunction and apoptosis. In this paper, we summarize and discuss the recent studies on the effects of certain important cytokines on pancreatic β-cell function. The imbalance in deleterious and protective cytokines plays pivotal roles in the development and progression of pancreatic β-cell dysfunction under insulin-resistant conditions.
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Affiliation(s)
- Chunjiong Wang
- Department of Physiology and Pathophysiology, Peking University Diabetes Center, Peking University Health Science Center, Beijing 100191, China
| | - Youfei Guan
- Department of Physiology and Pathophysiology, Peking University Diabetes Center, Peking University Health Science Center, Beijing 100191, China
| | - Jichun Yang
- Department of Physiology and Pathophysiology, Peking University Diabetes Center, Peking University Health Science Center, Beijing 100191, China
- *Jichun Yang:
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Filková M, Haluzík M, Gay S, Senolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin Immunol 2009; 133:157-70. [PMID: 19740705 DOI: 10.1016/j.clim.2009.07.013] [Citation(s) in RCA: 311] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2009] [Revised: 07/24/2009] [Accepted: 07/29/2009] [Indexed: 12/28/2022]
Abstract
Resistin was originally described as an adipocyte-secreted peptide that induced insulin resistance in rodents. Increasing evidence indicates its important regulatory roles in various biological processes, including several inflammatory diseases. Further studies have shown that resistin in humans, in contrast to its production by adipocytes in mice, is synthesized predominantly by mononuclear cells both within and outside adipose tissue. Possible roles for resistin in obesity-related subclinical inflammation, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, rheumatic diseases, malignant tumors, asthma, inflammatory bowel disease, and chronic kidney disease have already been demonstrated. In addition, resistin can modulate several molecular pathways involved in metabolic, inflammatory, and autoimmune diseases. In this review, current knowledge about the functions and pathophysiological implications of resistin in different human pathologies is summarized, although there is a significant lack of firm evidence regarding the specific role resistin plays in the "orchestra" of the numerous mediators of inflammation.
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Affiliation(s)
- Mária Filková
- Institute of Rheumatology and Connective Tissue Research Laboratory, Department of Rheumatology of First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Prague 2, 128 50, Czech Republic
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Gao CL, Zhao DY, Qiu J, Zhang CM, Ji CB, Chen XH, Liu F, Guo XR. Resistin induces rat insulinoma cell RINm5F apoptosis. Mol Biol Rep 2009; 36:1703-8. [PMID: 18839335 DOI: 10.1007/s11033-008-9371-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2008] [Accepted: 09/24/2008] [Indexed: 10/21/2022]
Abstract
Beta-cell apoptosis induced by adipokines may result in beta-cell dysfunction in type 2 diabetes. Resistin, an adipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells. Presently, the effects of resistin on rat insulinoma cells RINm5F were examined. Treatment of RINm5F with resistin induced cell damage. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) protected resistin-mediated cytotoxicity in RINm5F. Incubation with resistin up-regulated caspase-3 activity and induced the formation of a DNA ladder. TIMP-1 attenuated these effects. The molecular mechanism of TIMP-1 inhibition of resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IkB-alpha phosphorylation. Resistin treatment suppressed Akt phosphorylation and activated IkB-alpha phosphorylation, which could be attenuated by TIMP-1. We conclude that resistin can induce beta-cell apoptosis and that resistin-related beta-cell apoptosis can be prevented by TIMP-1.
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Affiliation(s)
- Chun-lin Gao
- Department of Pediatrics, Nanjing Maternity & Child Health Hospital of Nanjing Medical University, Nanjing, China
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Li M, Fisette A, Zhao XY, Deng JY, Mi J, Cianflone K. Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents. Int J Obes (Lond) 2009; 33:424-39. [PMID: 19290012 DOI: 10.1038/ijo.2009.44] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Resistin has been linked with obesity and hypothesized as a potential marker of insulin resistance in addition to being linked with acute inflammation. However, these links are still highly controversial in humans. Our goal was to examine resistin levels in relation to obesity, insulin resistance and inflammation markers in a large population of Asian children and adolescents. METHODS Children and adolescents (n=3472) aged 6-18 years, boys (n=1765) and girls (n=1707), were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, resistin, C-reactive protein (CRP), adiponectin and complement C3 (C3) levels. RESULTS Resistin increased with central obesity in both genders but not with simple adiposity in boys. Several markers associated with central obesity correlated in a gender-specific fashion with plasma resistin. Waist circumference, fat-mass percentage, waist-to-height ratio and body mass index (BMI) positively correlated with resistin in both genders. Blood lipids such as triglycerides, nonesterified fatty acids (NEFA) and low-density lipoprotein cholesterol, diastolic and systolic blood pressure correlated positively with resistin in boys. NEFA, high-density lipoprotein cholesterol (negatively) and inflammation markers, such as CRP and C3, positively correlated with resistin in girls. There was no correlation between resistin and adiponectin, and no association of adiponectin with resistin quintiles in either boys or girls. In both boys and girls, resistin tended to decrease with age, with girls having higher levels than boys. Few indices of insulin resistance were linked with plasma resistin in either gender. CONCLUSION In this population, plasma resistin levels are a weak biochemical marker of metabolic dysfunction defined by central obesity, adiposity and inflammation and does not predict insulin resistance. Only a small proportion of resistin variation can be explained by factors related to metabolic syndrome, suggesting that resistin is not strongly implicated in a concentration-dependent fashion in any of the examined pathologies.
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Affiliation(s)
- M Li
- Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, PR China
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Danielsson T, Fredriksson L, Jansson L, Henriksnäs J. Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized rats. Acta Physiol (Oxf) 2009; 195:283-8. [PMID: 18715288 DOI: 10.1111/j.1748-1716.2008.01891.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AIM Resistin is an adipokine which has been suggested to participate in the induction of insulin resistance associated with type 2 diabetes. The aim of the present study was to investigate whether acute administration of resistin influences tissue blood perfusion in rats. METHODS Resistin was administered as an intravenous infusion of 7.5 microg h(-1) (1.5 mL h(-1)) for 30 min to rats anaesthetized with thiobutabarbital. A microsphere technique was used to estimate the blood flow to six different depots of white adipose tissue (WAT), brown adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon, kidneys, adrenal glands and liver. RESULTS Resistin administration led to an increased blood flow to the pancreas and islets and a decrease in subcutaneous WAT and BAT. Intra-abdominal white adipose tissue blood flow and that to other organs were not affected. CONCLUSION Acute administration of resistin markedly affects the blood perfusion of both the pancreas and subcutaneous white adipose tissue depots. At present it is unknown whether resistin exerts a direct effect on the vasculature, or works through local or systemic activation of endothelial cells and/or macrophages. The extent to which this might contribute to the insulin resistance caused by resistin is yet unknown.
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Affiliation(s)
- T Danielsson
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
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Adrych K, Smoczynski M, Sledzinski T, Dettlaff-Pokora A, Goyke E, Swierczynski J. Increased serum resistin concentration in patients with chronic pancreatitis: possible cause of pancreatic fibrosis. J Clin Gastroenterol 2009; 43:63-8. [PMID: 18827713 DOI: 10.1097/mcg.0b013e31815cda0a] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Resistin is an adipokine, which displays proinflammatory properties. Thus, it is likely that resistin can influence the course of chronic pancreatitis, and/or that chronic pancreatitis may affect the serum resistin concentration. GOALS The aim of the present study was to determine the serum resistin concentration in patients with chronic pancreatitis and to analyze the relationship between serum resistin concentration and serum concentrations of leptin (proinflammatory adipokine) and adiponectin (anti-inflammatory adipokine). STUDY A total of 23 male, nondiabetic patients with chronic pancreatitis of alcoholic origin and 16 healthy subjects were examined. Fasting blood samples were collected from patients in both groups. Serum resistin concentration was assayed by enzyme-linked immunosorbent assay. Serum adiponectin, leptin, and insulin concentrations were determined by radioimmunoassay. RESULTS Serum resistin concentration was significantly higher in patients with chronic pancreatitis as compared with control subjects. In contrast, patients with chronic pancreatitis had lower serum leptin and insulin concentrations than healthy subjects. There were no statistically significant differences in serum adiponectin concentration between patients with pancreatitis and healthy subjects. CONCLUSIONS The results presented in this paper indicate that chronic pancreatitis in human is associated with the increase in serum resistin concentration and with the decrease in serum leptin and insulin concentrations. It can be supposed that resistin, by stimulation of tumor necrosis factor-alpha synthesis in blood mononuclear cells and in macrophages, increases the concentration of tumor necrosis factor-alpha, which in turn activates stellate cells. Activated stellate cells can produce collagen, eventually resulting in the development of pancreatic fibrosis.
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Affiliation(s)
- Krystian Adrych
- Department of Gastroenterology and Hepatology, Medical University of Gdansk, Gdansk, Poland
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Forsblad d'Elia H, Pullerits R, Carlsten H, Bokarewa M. Resistin in serum is associated with higher levels of IL-1Ra in post-menopausal women with rheumatoid arthritis. Rheumatology (Oxford) 2008; 47:1082-1087. [PMID: 18511473 DOI: 10.1093/rheumatology/ken187] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2024] Open
Abstract
OBJECTIVES The aim of this study was to investigate associations between serum levels of resistin, an adipokine and markers of inflammation, bone metabolism, plasma lipids and kidney function in post-menopausal RA patients and to evaluate if HRT during 2 yrs affected resistin levels. METHODS Eighty-eight women were randomly allocated to receive HRT, vitamin D(3) and calcium or vitamin D(3) and calcium alone. Serum levels of resistin, IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-6 soluble receptor, TNF-alpha were measured by ELISA, markers of bone metabolism, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen by RIA, ESR, CRP, Hb, creatinine and lipids by standard laboratory techniques, BMD and total lean mass (TLM) by DXA and joint destruction by Larsen score. Resistin was also measured in 42 healthy control women. RESULTS There was no difference in resistin concentration between patients and healthy controls. Resistin was significantly correlated with IL-1Ra, CRP, TNF-alpha, ICTP, glucocorticosteroids and Larsen score and inversely with BMD, hip and with TLM. In multiple regression analysis, IL-1Ra, TLM and use of corticosteroids remained determinants of resistin. Patients treated with HRT displayed significant increase in resistin compared with controls in the first but not the second year. CONCLUSIONS Resistin was associated with increased inflammation, particularly by the acute-phase reactant IL-1Ra antagonizing IL-1beta, joint destruction, glucocorticosteroids and with reduced BMD and TLM. These findings suggest resistin being a significant mediator in the inflammatory process in RA. Further studies examining the mechanisms behind the relation between resistin and IL-1Ra are encouraged. HRT does not seem to have important long-term effect on resistin.
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Affiliation(s)
- H Forsblad d'Elia
- Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden.
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Qiao XZ, Wang XF, Xu ZR, Yang YM. Resistin does not down-regulate the transcription of insulin receptor promoter. J Zhejiang Univ Sci B 2008; 9:313-8. [PMID: 18381806 DOI: 10.1631/jzus.b0710637] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To detect the effect of resistin on the transcription of insulin receptor promoter. METHODS Luciferase reporter gene was fused downstream of human insulin receptor promoter and the enzymatic activity of luciferase was determined in the presence or absence of resistin. The resistin expressed with plasmid was stained with antibody against Myc tag which was in frame fused with resistin coding sequence, and then imaged with confocal microscopy. RESULTS The treatment of pIRP-LUC transfected cells with recombinant resistin did not result in significant difference in the enzymatic activity of luciferase compared to the untreated cells. Cell staining showed that green fluorescence could be observed in the cytoplasm, but not in the nucleus. CONCLUSION The results suggest that the endogenous resistin may functionally locate in the cytoplasm, but does not enter the nucleus and not down-regulate the transcription of insulin receptor promoter.
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Affiliation(s)
- Xiao-zhi Qiao
- Department of Very Important Person, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
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Abstract
The healthy beta-cell has an enormous capacity to adapt to conditions of higher insulin demand (e.g. in obesity, pregnancy, cortisol excess) to maintain normoglycaemia with an increase in its functional beta-cell mass. This compensates in 80-90% of individuals for insulin resistance. However, in 10-20% of individuals, the beta-cells are unable to match the demands of insulin resistance and insulin levels are relatively insufficient to maintain normal glycaemic control. This eventually leads to glucose intolerance and type 2 diabetes (T2DM). Accordingly, preservation of functional beta-cell mass has become central in the treatment of type 1 diabetes as well as T2DM. The purpose of this review is to summarize the recently described mechanisms of beta-cell death in T2DM and to postulate possible new targets for treatment.
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Affiliation(s)
- Kathrin Maedler
- Department of Medicine, Larry L. Hillblom Islet Research Center, University of California at Los Angeles, Los Angeles, CA 90095-7345, USA.
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Park S, Hong SM, Sung SR, Jung HK. Long-term effects of central leptin and resistin on body weight, insulin resistance, and beta-cell function and mass by the modulation of hypothalamic leptin and insulin signaling. Endocrinology 2008; 149:445-54. [PMID: 17991727 DOI: 10.1210/en.2007-0754] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
To determine the long-term effect of central leptin and resistin on energy homeostasis, peripheral insulin resistance, and beta-cell function and mass, intracerebroventricular (ICV) infusion of leptin (3 ng/h), resistin (80 ng/h), leptin plus resistin, and cerebrospinal fluid (control) was conducted by means of an osmotic pump for 4 wk on normal rats and 90% pancreatectomized diabetic rats fed 40% fat-energy diets. Overall, the effects were greater in diabetic rats than normal rats. Leptin infusion, causing a significant reduction in food intake, decreased body weight and epididymal fat. However, resistin and leptin plus resistin reduced epididymal fat with decreased serum leptin levels in comparison with the control. Unlike serum leptin, only resistin infusion lowered serum resistin levels. Central leptin increased glucose infusion rates during euglycemic hyperinsulinemic clamp and suppressed hepatic glucose production in the hyperinsulinemic state in comparison with the control. However, central leptin did not affect glucose-stimulated insulin secretion and beta-cell mass. Central resistin infusion also increased peripheral insulin sensitivity, but not as much as leptin. Unlike leptin, resistin significantly increased first-phase insulin secretion during hyperglycemic clamp and beta-cell mass by augmenting beta-cell proliferation. These metabolic changes were associated with hypothalamic leptin and insulin signaling. ICV infusion of leptin potentiated signal transducer and activator of transcription 3 phosphorylation and attenuated AMP kinase in the hypothalamus, but resistin had less potent effects than leptin. Leptin enhanced insulin signaling by potentiating IRS2-->Akt pathways, whereas resistin activated Akt without augmenting insulin receptor substrate 2 phosphorylation. In conclusion, long-term ICV infusion of leptin and resistin independently improved energy and glucose homeostasis by modulating in different ways hypothalamic leptin and insulin signaling.
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Affiliation(s)
- Sunmin Park
- Department of Food and Nutrition, Hoseo University, Asan-Si, Chungnam-Do, Korea.
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47
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48
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Kim SJ, Nian C, McIntosh CHS. Resistin Is a Key Mediator of Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Lipoprotein Lipase (LPL) Activity in Adipocytes. J Biol Chem 2007; 282:34139-47. [PMID: 17890220 DOI: 10.1074/jbc.m704896200] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Studies on the physiological roles of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP) have largely focused on its insulinotropic action and ability to regulate beta-cell mass. In previous studies on the stimulatory effect of GIP on adipocyte lipoprotein lipase (LPL), a pathway was identified involving increased phosphorylation of protein kinase B (PKB) and reduced phosphorylation of LKB1 and AMP-activated protein kinase (AMPK). The slow time of onset of the responses suggested that GIP may have induced release of an intermediary molecule, and the current studies focused on the possible contribution of the adipokine resistin. In differentiated 3T3-L1 adipocytes, GIP, in the presence of insulin, increased resistin secretion through a pathway involving p38 mitogen-activated protein kinase (p38 MAPK) and the stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK). The other major incretin hormone, glucagon-like peptide-1 (GLP-1), exhibited no significant effects. Chronic elevation of circulating GIP levels in the Vancouver Diabetic Fatty (VDF) Zucker rat resulted in increases in circulating resistin levels and activation of p38 MAPK or SAPK/JNK in epididymal fat tissue, suggesting the existence of identical pathways in vivo as well as in vitro. Administration of resistin to 3T3-L1 adipocytes mimicked the effects of GIP on the PKB/LKB1/AMPK/LPL pathway: increasing phosphorylation of PKB, reducing levels of phosphorylated LKB1 and AMPK, and increasing LPL activity. Knockdown of resistin using RNA interference attenuated the effect of GIP on the PKB/LKB1/AMPK/LPL pathway in 3T3-L1 adipocytes, supporting a role for resistin as a mediator.
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Affiliation(s)
- Su-Jin Kim
- Department of Cellular and Physiological Sciences and the Diabetes Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
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Brown JEP, Onyango DJ, Dunmore SJ. Resistin down-regulates insulin receptor expression, and modulates cell viability in rodent pancreatic beta-cells. FEBS Lett 2007; 581:3273-6. [PMID: 17597619 DOI: 10.1016/j.febslet.2007.06.031] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2007] [Accepted: 06/12/2007] [Indexed: 02/05/2023]
Abstract
The adipokine resistin is known to induce insulin resistance in rodent tissues. Increases in adipose tissue mass are known to have a negative effect on pancreatic beta-cell function, although the mechanisms are poorly understood. This study investigated the effects of resistin on insulin secretion, insulin receptor expression and cell viability in pancreatic beta-cells. BTC-6 or BRIN-BD11 cells were treated for 24h with resistin, and insulin receptor expression, insulin secretion and cell viability were measured. Incubation with 40ng/ml resistin caused significant decreases in insulin receptor mRNA and protein expression, but did not affect insulin secretion. At low concentrations, resistin caused significant increases in cell viability. These data implicate resistin as a factor that may regulate beta-cell function/viability, and suggests a potential mechanism by which increased adiposity causes beta-cell dysfunction.
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Affiliation(s)
- James E P Brown
- Diabetes and Metabolic Disorders Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Wolverhampton, UK.
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50
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Thommesen L, Stunes AK, Monjo M, Grøsvik K, Tamburstuen MV, Kjøbli E, Lyngstadaas SP, Reseland JE, Syversen U. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem 2007; 99:824-34. [PMID: 16721825 DOI: 10.1002/jcb.20915] [Citation(s) in RCA: 147] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The adipose tissue is the site of expression and secretion of a range of biologically active proteins, called adipokines, for example, leptin, adiponectin, and resistin. Leptin has previously been shown to be expressed in osteoblasts and to promote bone mineralization, whereas adiponectin expression is enhanced during osteoblast differentiation. In the present study we explored the possible role of resistin in bone metabolism. We found that resistin is expressed in murine preosteoclasts and preosteoblasts (RAW 264.7, MC3T3-E1), in primary human bone marrow stem cells and in mature human osteoblasts. The expression of resistin mRNA in RAW 264.7 was increased during differentiation and seemed to be regulated through PKC- and PKA-dependent mechanisms. Recombinant resistin increased the number of differentiated osteoclasts and stimulated NFkappaB promoter activity, indicating a role in osteoclastogenesis. Resistin also enhanced the proliferation of MC3T3-E1 cells in a PKA and PKC-dependent manner, but only weakly interfered with genes known to be upregulated during differentiation of MC3T3-E1 into osteoblasts. All together, our results indicate that resistin may play a role in bone remodeling.
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Affiliation(s)
- Liv Thommesen
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
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