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Sharafi SM, Yazdi M, Goodarzi-Khoigani M, Kelishadi R. Effect of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D and Homeostatic Model of Insulin Resistance Levels in Healthy Pregnancy: A Systematic Review and Meta-Analysis. IRANIAN JOURNAL OF MEDICAL SCIENCES 2023; 48:4-12. [PMID: 36688198 PMCID: PMC9843454 DOI: 10.30476/ijms.2021.90586.2166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/16/2021] [Accepted: 11/01/2021] [Indexed: 01/24/2023]
Abstract
Background Progressive insulin resistance is a physiological condition during pregnancy that can lead to gestational diabetes. Given the association between low blood vitamin D levels and insulin resistance, the present meta-analysis evaluated the effect of vitamin D supplementation on serum 25-hydroxyvitamin D (25[OH]D) and the homeostatic model of insulin resistance (HOMA-IR) levels in non-diabetic pregnant women. Methods A comprehensive literature search was conducted using electronic databases and gateways such as Cochrane Library, Medline, Google Scholar, Science Direct, Web of Sciences, Embase, and Scopus. Articles up to 2020 in both English and Persian were included in the study. The effect of vitamin D supplementation on 25(OH)D and HOMA-IR was determined based on the differences in mean changes from baseline to post-intervention. Weighted mean and 95% confidence intervals (CI) were pooled using a random-effects model. Data were analyzed using STATA software. Results Four studies, including six trials with 380 participants, reported that vitamin D supplementation increased 25(OH)D (mean change: 13.72, 95% CI: 7.28-20.17) and decreased HOMA-IR (mean change: 1.46, 95% CI: 0.56-2.37) levels compared with the placebo group. A high weekly dose of vitamin D further reduced HOMA-IR levels (adjusted R2=77.99, I2 residuals=80.49%, P=0.047). There was no significant association between the dose of vitamin D and 25(OH)D (P=0.974). Intervention duration was not associated with an increase in 25(OH)D (P=0.102), nor with a decrease in HOMA-IR (P=0.623). Conclusion Vitamin D supplementation increased 25(OH)D and decreased HOMA-IR levels in non-diabetic pregnant women. Vitamin D in high doses further reduced HOMA-IR, but did not affect 25(OH)D concentrations.
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Affiliation(s)
- Seyedeh Maryam Sharafi
- Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Yazdi
- Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoomeh Goodarzi-Khoigani
- Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Roya Kelishadi
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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Mirzaei-Azandaryani Z, Mohammad-Alizadeh-Charandabi S, Shaseb E, Abbasalizadeh S, Mirghafourvand M. Effects of vitamin D on insulin resistance and fasting blood glucose in pregnant women with insufficient or deficient vitamin D: a randomized, placebo-controlled trial. BMC Endocr Disord 2022; 22:254. [PMID: 36266683 PMCID: PMC9585796 DOI: 10.1186/s12902-022-01159-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 09/28/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gestational diabetes is one of the most common metabolic disorders during pregnancy. Some studies have reported the effect of vitamin D deficiency on the incidence of this disorder. Therefore, the purpose of the present study was to determine the effect of vitamin D supplementation on fasting blood glucose (FBG) levels, fasting blood insulin (FBI) levels and insulin resistance index (HOMA-IR) (primary outcomes) and symptoms of depression, musculoskeletal pain, frequency of gestational diabetes and the frequency of abortion (secondary outcomes). METHODS In this triple-blind randomized controlled trial, 88 pregnant women at 8-10 weeks of pregnancy who had the vitamin D of less than 30 ng/ml were randomly assigned to the vitamin D group (n = 44) and control group (n = 44) using block randomization. The vitamin D group received 4,000 units of vitamin D tablets daily and the control group received placebo tablets for 18 weeks. Independent t-test, Mann-Whitney U and ANCOVA tests were used to analyze the data. RESULTS After the intervention, there was no statistically significant difference between the two groups in terms of FBG (P = 0.850), FBI (P = 0.353), HOMA-IR (P = 0.632), mean score of depressive symptoms (P = 0.505), frequency of gestational diabetes (P = 0.187) and frequency of abortion (P = 1.000) and there was only a difference in terms of serum vitamin D level (P = 0.016) and musculoskeletal pain including knee pain (P = 0.025), ankle pain (P < 0.001) and leg pain (P < 0.001). CONCLUSION Vitamin D could improve the musculoskeletal pain in pregnant women but couldn't decrease FBG, FBI, HOMA-IR, depression symptoms score, incidence of GDM and abortion. TRIAL REGISTRATION Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N59. Date of registration: 4/11/2020. URL: https://en.irct.ir/user/trial/50973/view ; Date of first registration: 21/11/2020.
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Affiliation(s)
- Zahra Mirzaei-Azandaryani
- Students’ research committee, Nursing and Midwifery Faculty, Social Determinants of Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Elnaz Shaseb
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shamsi Abbasalizadeh
- Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mojgan Mirghafourvand
- Social Determinants of Health Research Center, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
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Cai F, Hu C, Chen CJ, Han YP, Lin ZQ, Deng LH, Xia Q. Vitamin D and Pancreatitis: A Narrative Review of Current Evidence. Nutrients 2022; 14:nu14102113. [PMID: 35631254 PMCID: PMC9143310 DOI: 10.3390/nu14102113] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/12/2022] [Accepted: 05/13/2022] [Indexed: 12/10/2022] Open
Abstract
Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.
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Affiliation(s)
- Fei Cai
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Cheng Hu
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Chan-Juan Chen
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Yuan-Ping Han
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China;
| | - Zi-Qi Lin
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Li-Hui Deng
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
- Correspondence:
| | - Qing Xia
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
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Brosolo G, Da Porto A, Bulfone L, Scandolin L, Vacca A, Bertin N, Vivarelli C, Sechi LA, Catena C. Vitamin D Deficiency Is Associated with Glycometabolic Changes in Nondiabetic Patients with Arterial Hypertension. Nutrients 2022; 14:nu14020311. [PMID: 35057492 PMCID: PMC8778458 DOI: 10.3390/nu14020311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/07/2022] [Accepted: 01/10/2022] [Indexed: 11/16/2022] Open
Abstract
Recent evidence indicates that mildly increased fasting and post-oral load blood glucose concentrations contribute to development of organ damage in nondiabetic patients with hypertension. In previous studies, vitamin D deficiency was associated with decreased glucose tolerance. The aim of this study was to examine the relationships between serum 25(OH)D levels and glucose tolerance and insulin sensitivity in hypertension. In 187 nondiabetic essential hypertensive patients free of cardiovascular or renal complications, we measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and performed a standard oral glucose tolerance test (OGTT). Patients with 25(OH)D deficiency/insufficiency were older and had significantly higher blood pressure, fasting and post-OGTT (G-AUC) glucose levels, post-OGTT insulin (I-AUC), PTH levels, and prevalence of metabolic syndrome than patients with normal serum 25(OH)D. 25(OH)D levels were inversely correlated with age, blood pressure, fasting glucose, G-AUC, triglycerides, and serum calcium and PTH, while no significant relationships were found with body mass index (BMI), fasting insulin, I-AUC, HOMA index, and renal function. In a multivariate regression model, greater G-AUC was associated with lower 25(OH)D levels independently of BMI and seasonal vitamin D variations. Thus, in nondiabetic hypertensive patients, 25(OH)D deficiency/insufficiency could contribute to impaired glucose tolerance without directly affecting insulin sensitivity.
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Liu Y, Guo X, Huang SY, Gong L, Cui JH, Shen HW, Ye XH, He XF. Evaluation of association studies and a systematic review and meta-analysis of VDR polymorphisms in type 2 diabetes mellitus risk. Medicine (Baltimore) 2021; 100:e25934. [PMID: 34260520 PMCID: PMC8284732 DOI: 10.1097/md.0000000000025934] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 04/15/2021] [Accepted: 04/17/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor (VDR) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues.To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk.PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: (VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test.Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries.On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association.In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.
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Affiliation(s)
- Yao Liu
- Changzhi Medical College, No. 161, JieFangDong Street
| | - Xin Guo
- Changzhi Medical College, No. 161, JieFangDong Street
| | | | - Luan Gong
- Changzhi Medical College, No. 161, JieFangDong Street
| | - Jin-Hui Cui
- Changzhi Medical College, No. 161, JieFangDong Street
| | - Hu-Wei Shen
- Department of Endocrinology, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi city
| | - Xiang-Hua Ye
- Department of Radiotherapy, First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou city
| | - Xiao-Feng He
- Institute of Evidence-Based Medicine, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi city, PR China
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Wu J, Shao B, Xin X, Luo W, Mo M, Jiang W, Si S, Wang S, Shen Y, Yu Y. Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement. Clin Nutr 2021; 40:3650-3660. [PMID: 33423808 DOI: 10.1016/j.clnu.2020.12.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 11/05/2020] [Accepted: 12/21/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND & AIMS This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.
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Affiliation(s)
- Jinhua Wu
- Zhoushan Maternal and Child Care Hospital, Zhoushan, China
| | - Bule Shao
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xing Xin
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenliang Luo
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Minjia Mo
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wen Jiang
- Zhoushan Maternal and Child Care Hospital, Zhoushan, China
| | - Shuting Si
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shuojia Wang
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yu Shen
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yunxian Yu
- Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.
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Rafiq S, Jeppesen PB. Body Mass Index, Vitamin D, and Type 2 Diabetes: A Systematic Review and Meta-Analysis. Nutrients 2018; 10:nu10091182. [PMID: 30154381 PMCID: PMC6164132 DOI: 10.3390/nu10091182] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Revised: 08/22/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
The deficiency of vitamin D is prevalent all over the world. Studies have shown that vitamin D may play an important role in the development of obesity. The current study was conducted to quantitatively evaluate the association between serum 25-(OH) vitamin D levels and the risk of obesity in both diabetic and non-diabetic subjects. A systematic review and meta-analysis of observational studies was carried out for that purpose. We searched the Medline, PubMed, and Embase databases throughout all of March 2018. A total of fifty five observational studies for both diabetic and non-diabetic subjects were finally included in the meta-analysis. The data were analyzed by comprehensive meta-analysis software version 3 and the random effects model was used to analyze the data. The meta-analysis showed an overall inverse relationship between serum vitamin D status and body mass index (BMI) in studies of both diabetic (r = −0.173, 95% = −0.241 to −0.103, p = 0.000) and non-diabetic (r = −0.152, 95% = −0.187 to −0.116, p = 0.000) subjects. The evidence of publication bias was not found in this meta-analysis. In conclusion, the deficiency of vitamin D is associated with an increased level of BMI in the studies of both diabetic and non-diabetic subjects. Reliable evidence from well-designed future randomized controlled trials is required to confirm the findings from observational studies and to find out the potential regulatory effects of vitamin D supplementation to lower BMI.
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Affiliation(s)
- Shamaila Rafiq
- Department of Clinical Medicine Aarhus University, 8200 Aarhus, Denmark.
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Bertoccini L, Sentinelli F, Leonetti F, Bailetti D, Capoccia D, Cimini FA, Barchetta I, Incani M, Lenzi A, Cossu E, Cavallo MG, Baroni MG. The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus. Endocr Res 2017; 42:331-335. [PMID: 28388281 DOI: 10.1080/07435800.2017.1305965] [Citation(s) in RCA: 6] [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: 12/21/2022]
Abstract
AIM Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls. MATERIALS AND METHODS For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated. RESULTS Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes. CONCLUSIONS Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.
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Affiliation(s)
- Laura Bertoccini
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Federica Sentinelli
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Frida Leonetti
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Diego Bailetti
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Danila Capoccia
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Flavia A Cimini
- b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy
| | - Ilaria Barchetta
- b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy
| | - Michela Incani
- c Endocrinology and Diabetes, Department of Medical Sciences , University of Cagliari , Cagliari , Italy
| | - Andrea Lenzi
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
| | - Efisio Cossu
- c Endocrinology and Diabetes, Department of Medical Sciences , University of Cagliari , Cagliari , Italy
| | - M Gisella Cavallo
- b Internal Medicine Unit, Department of Internal Medicine and Medical Specialties , Sapienza University of Rome , Rome , Italy
| | - Marco G Baroni
- a Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy
- d IRCCS Neuromed , Pozzilli
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10
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Uwaezuoke SN. Vitamin D deficiency and anemia risk in children: a review of emerging evidence. Pediatric Health Med Ther 2017; 8:47-55. [PMID: 29388633 PMCID: PMC5774601 DOI: 10.2147/phmt.s129362] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
There has been renewed scientific interest in the sequelae of vitamin D deficiency, given the emerging evidence on the diverse biologic functions of vitamin D, besides its fundamental role in bone and mineral metabolism. For the past decade, the evidence in the medical literature pointing to a relationship between anemia risk and vitamin D deficiency has been accumulating. This paper critically reviews the current evidence linking vitamin D deficiency to anemia risk in children. The synthesized evidence indicates that the studies, which were preponderantly conducted among the adult population, not only reported a bidirectional relationship between vitamin D deficiency and anemia but also showed a racial effect. In studies conducted among children, similar results were reported. Although the causal association of vitamin D deficiency with anemia risk (especially iron-deficiency anemia) remains debatable, the noncalcemic actions of the vitamin and its analogs hold prospects for several novel clinical applications. There is, however, unanimity in many reports suggesting that vitamin D deficiency is directly associated with anemia of chronic disease or inflammation. Despite the advances in unraveling the role of vitamin D in iron homeostasis, further research is still required to validate causality in the relationship between vitamin D deficiency and anemia, as well as to determine its optimal dosing, the ideal recipients for therapeutic intervention, and the preferred analogs to administer.
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Affiliation(s)
- Samuel N Uwaezuoke
- Department of Paediatrics, College of Medicine, University of Nigeria, Nsukka
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
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Relationship between cardiometabolic profile, vitamin D status and BsmI polymorphism of the VDR gene in non-institutionalized elderly subjects. Exp Gerontol 2016; 81:56-64. [DOI: 10.1016/j.exger.2016.04.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 04/12/2016] [Accepted: 04/24/2016] [Indexed: 12/15/2022]
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Sentinelli F, Bertoccini L, Barchetta I, Capoccia D, Incani M, Pani MG, Loche S, Angelico F, Arca M, Morini S, Manconi E, Lenzi A, Cossu E, Leonetti F, Baroni MG, Cavallo MG. The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children. Nutr Metab Cardiovasc Dis 2016; 26:407-413. [PMID: 27052925 DOI: 10.1016/j.numecd.2016.02.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 12/30/2015] [Accepted: 02/01/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIMS 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. METHODS AND RESULTS As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of β-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. CONCLUSIONS Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.
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Affiliation(s)
- F Sentinelli
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - L Bertoccini
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - I Barchetta
- Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - D Capoccia
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - M Incani
- Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy
| | - M G Pani
- Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy
| | - S Loche
- Pediatric Endocrine Unit, Regional Hospital for Microcitemia, Cagliari, Italy
| | - F Angelico
- Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - M Arca
- Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - S Morini
- Human Anatomy, (CIR), University Campus Bio-Medico, Rome, Italy
| | - E Manconi
- Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy
| | - A Lenzi
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - E Cossu
- Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy
| | - F Leonetti
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - M G Baroni
- Department of Experimental Medicine, Sapienza University of Rome, Italy; Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
| | - M G Cavallo
- Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
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Bal M, Şahin Ersoy G, Demirtaş Ö, Kurt S, Taşyurt A. Vitamin D deficiency in pregnancy is not associated with diabetes mellitus development in pregnant women at low risk for gestational diabetes. Turk J Obstet Gynecol 2016; 13:23-26. [PMID: 28913084 PMCID: PMC5558351 DOI: 10.4274/tjod.10170] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 01/17/2016] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE We aimed to investigate the effect of vitamin D deficiency as a risk factor for the development of gestational diabetes mellitus (GDM) among pregnant women without known risk factors. MATERIALS AND METHODS The study was conducted on pregnant women who had been under regular follow-up and had low risk for GDM development. The patients were divided into two groups according to the presence of GDM; GDM and no GDM (control) group. Body mass index (BMI), sociodemographic data including level of education and nutritional habits were recorded. Serum 25 (OH) vitamin D3 levels, hemoglobin, hematocrit, and mean corpuscular volume (MCV) values were measured. An oral glucose tolerance test was performed, between 24 and 28 weeks of pregnancy. RESULTS GDM ratio was calculated as 4.6%. The false positive rate of 50 g oral glucose load screening test was found to be 16.5%. The BMI levels of women diagnosed as having GDM and those with no GDM group at the beginningof the pregnancy period were calculated as 24.3±2.6 and 22.8±1.6 kg/m2 respectively, exhibiting a statistically significant difference between the two groups (p=0.001). Hemoglobin, hematocrit, and MCV values did not show a statistically significant difference between the two groups (p>0.05). The levels of 25 (OH) vitamin D3 of the study groups were found comparable in both groups (p=0.13). CONCLUSION Plasma levels of vitamin D may not be a contributing factor for the development of GDM in women with a low risk for GDM.
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Affiliation(s)
- Mehmet Bal
- Tepecik Education and Research Hospital, Department of Obstetrics and Gynecology, İzmir, Turkey
| | - Gülçin Şahin Ersoy
- Tepecik Education and Research Hospital, Department of Obstetrics and Gynecology, İzmir, Turkey
| | - Ömer Demirtaş
- Tepecik Education and Research Hospital, Department of Obstetrics and Gynecology, İzmir, Turkey
| | - Sefa Kurt
- Tepecik Education and Research Hospital, Department of Obstetrics and Gynecology, İzmir, Turkey
| | - Abdullah Taşyurt
- Tepecik Education and Research Hospital, Department of Obstetrics and Gynecology, İzmir, Turkey
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Mitchell DM, Leder BZ, Cagliero E, Mendoza N, Henao MP, Hayden DL, Finkelstein JS, Burnett-Bowie SAM. Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. Am J Clin Nutr 2015; 102:385-92. [PMID: 26156733 PMCID: PMC4515870 DOI: 10.3945/ajcn.115.111682] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 06/04/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. OBJECTIVE The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total). DESIGN This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. RESULTS On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI. CONCLUSION In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health.
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Affiliation(s)
| | | | | | | | | | - Douglas L Hayden
- Biostatistics Center, Massachusetts General Hospital, Boston, MA
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Stadlmayr A, Aigner E, Huber-Schönauer U, Niederseer D, Zwerina J, Husar-Memmer E, Hohla F, Schett G, Patsch W, Datz C. Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians. Acta Diabetol 2015; 52:39-46. [PMID: 24849007 DOI: 10.1007/s00592-014-0596-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 05/05/2014] [Indexed: 11/28/2022]
Abstract
Vitamin D (Vit D) deficiency may be linked to the development of obesity-associated complications such as insulin resistance and type 2 diabetes. We therefore evaluated the relationship of Vit D serum concentrations with metabolic parameters and type 2 diabetes in middle-aged Caucasian men and women. One thousand six hundred and thirty-one Caucasians (832 males, 58.8 ± 9.7 years; 799 females, 59.7 ± 10.7 years) were evaluated in a cross-sectional study. Vit D status was assessed by measuring the serum concentration of 25-hydroxyvitamin D3 [25(OH)D3]. Type 2 diabetes prevalence was ascertained by medical history, fasting plasma glucose concentrations, oral glucose tolerance testing and/or glycosylated hemoglobin. Men displayed higher crude or seasonally adjusted 25(OH)D3 serum concentrations than women (24.64 ± 10.98 vs. 22.88 ± 11.6 ng/ml; P < 0.001). Strong associations between body mass index (BMI) and 25(OH)D3 were observed in both genders (P < 0.001). Seasonally adjusted levels of 25(OH)D3 revealed stronger associations with type 2 diabetes in women than men (P < 0.001). However, adjustment for BMI and other confounding variables revealed an independent inverse association of 25(OH)D3 with diabetes only in women (P < 0.001), whereas the association was abrogated in men. Using a 15 ng/ml 25(OH)D3 cutoff for binary comparison, adjusted odds ratios for having newly diagnosed or known type 2 diabetes more than doubled (2.95 [95 % CI 1.37-4.89] and 3.26 [1.59-6.68], respectively), in women below the cutoff. We conclude that in women, but not in men, low 25(OH)D3 serum levels are independently associated with type 2 diabetes. These findings suggest sex-specific effects of Vit D in the pathogenesis of type 2 diabetes.
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Affiliation(s)
- Andreas Stadlmayr
- Department of Internal Medicine, Oberndorf Hospital, Teaching Hospital of the Paracelsus Medical University Salzburg, Paracelsusstraße 37, Oberndorf, 5110, Austria
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Reinert-Hartwall L, Honkanen J, Härkönen T, Ilonen J, Simell O, Peet A, Tillmann V, Lamberg-Allardt C, Virtanen SM, Knip M, Vaarala O. No association between vitamin D and β-cell autoimmunity in Finnish and Estonian children. Diabetes Metab Res Rev 2014; 30:749-60. [PMID: 24692218 DOI: 10.1002/dmrr.2550] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/14/2014] [Accepted: 03/14/2014] [Indexed: 01/03/2023]
Abstract
BACKGROUND Vitamin D has immunomodulatory properties, such as regulation of FOXP3 expression and regulatory T-cell activity. Our aim was to investigate whether plasma 25-hydroxyvitamin D [25(OH)D] concentrations associate with the development of β-cell autoimmunity and the transcriptional activity of FOXP3 or vitamin D3 convertase gene (CYP27B1) in CD4+ memory T cells. METHODS We studied 83 Finnish and 32 Estonian children participating in the DIABIMMUNE and DIPP studies. Twenty-nine Finnish and six Estonian children tested positive for at least one diabetes-associated autoantibody. The plasma concentrations of 25(OH)D and 1,25(OH)₂D were analysed with an enzyme immunoassay. Gene expression of FOXP3 and CYP27B1 in the isolated CD4+ memory T cells was studied with reverse transcription quantitative polymerase chain reaction. RESULTS Vitamin D status did not differ between subjects positive and negative for β-cell autoantibodies. Finnish children had higher vitamin D status than Estonian children (p < 0.001). FOXP3 expression was higher in Estonian CD4+ memory T-cell samples than in Finnish samples (p < 0.01) even when including in both groups only children with serum 25(OH)D concentrations in the range of 50-80 nmol/L (p < 0.001). CONCLUSIONS These findings do not support a crucial role of circulating 25(OH)D as a regulator of β-cell autoimmunity or FOXP3 expression.
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Affiliation(s)
- L Reinert-Hartwall
- Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland
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Sciacqua A, Perticone M, Grillo N, Falbo T, Bencardino G, Angotti E, Arturi F, Parlato G, Sesti G, Perticone F. Vitamin D and 1-hour post-load plasma glucose in hypertensive patients. Cardiovasc Diabetol 2014; 13:48. [PMID: 24555478 PMCID: PMC3931918 DOI: 10.1186/1475-2840-13-48] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 02/14/2014] [Indexed: 02/06/2023] Open
Abstract
Background A plasma glucose value ≥155 mg/dl for 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes and with subclinical organ damage. We designed this study to address if 25-hydroxyvitamin D [25(OH)D] circulating levels are associated with glucose tolerance status, and in particular with 1-hour post-load plasma glucose levels. Methods We enrolled 300 consecutive Caucasian hypertensive never-treated outpatients (160 men and 140 women, aged 52.9 ± 9.2 years). Subjects underwent OGTT and measurements of 25(OH)D and standard laboratory tests. Estimated glomerular filtration rate (e-GFR) was calculated by CKD-EPI formula and insulin sensitivity was assessed by Matsuda-index. Results Among participants, 230 were NGT, 44 had impaired glucose tolerance (IGT) and 26 had type-2 diabetes. According to 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into: NGT < 155 (n = 156) and NGT > 155 mg/dL (n = 74). NGT ≥ 155 had higher significant fasting and post-load glucose and insulin, parathyroid hormone and hs-CRP levels than NGT < 155. On the contrary, Matsuda-index, e-GFR, and 25(OH)D were significantly lower in NGT ≥ 155 than NGT < 155 subjects. In the multiple regression analysis, 25(OH)D levels resulted the major determinant of 1-h post-load plasma glucose in all population and in the four groups of glucose tolerance status. In the whole population, Matsuda-index, hs-CRP and e-GFR explained another 12.2%, 6.7% and 1.7% of its variation. Conclusions Our data demonstrate a significant and inverse relationship between 25(OH)D levels and glucose tolerance status, particularly with 1-h post-load glucose.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V,le Europa 88100, Catanzaro, Italy.
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Vejrazkova D, Vcelak J, Vankova M, Lukasova P, Bradnova O, Halkova T, Kancheva R, Bendlova B. Steroids and insulin resistance in pregnancy. J Steroid Biochem Mol Biol 2014. [PMID: 23202146 DOI: 10.1016/j.jsbmb.2012.11.007] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Metabolism of glucose during pregnancy reflects the equilibrium between lactogenic hormones stimulating insulin production and counterregulatory hormones inducing insulin resistance. In physiological pregnancies, insulin-mediated glucose uptake is substantially decreased and insulin secretion increased to maintain euglycemia. This common state of peripheral insulin resistance arises also due to steroid spectra changes. In this review article, we have focused on the role of steroid hormones (androgens, estrogens, gestagens, mineralocorticoids, glucocorticoids, as well as secosteroid vitamin D) in the impairment of glucose tolerance in pregnancy and in the pathogenesis of gestational diabetes mellitus. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.
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Stumpf WE. Whole-body and microscopic autoradiography to determine tissue distribution of biopharmaceuticals -- target discoveries with receptor micro-autoradiography engendered new concepts and therapies for vitamin D. Adv Drug Deliv Rev 2013; 65:1086-97. [PMID: 23391491 DOI: 10.1016/j.addr.2012.11.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 11/27/2012] [Accepted: 11/27/2012] [Indexed: 11/16/2022]
Abstract
Information about the distribution of biopharmaceuticals is basic for understanding their actions. Tissue and cellular localization is a key to function. Autoradiography with radiolabeled compounds has provided valuable information with both low resolution whole-body macro-autoradiography and high resolution microscopic autoradiography (micro-autoradiography). Whole-body macro-autoradiography is a uniform and expedient single method approach, providing convenient dose- and time-related overviews with data similar to those obtained with conventional bioassays - and therefore widely used. However, whole-body macro-autoradiography, like common bioassays, has limitations. High specificity-low capacity sites of binding and deposition frequently remain unrecognized. Lack of cellular resolution can cause false negatives and provide misleading results (e.g., false blood-brain barrier). For micro-autoradiography, different methods are advertised in the literature. Most of them are, however, unsuited for drug localization because of inadequate resolution and frequent artifacts. Most drugs interact with their receptors non-covalently by weak electrostatic forces. Therefore, translocation and loss can occur during tissue preparation. This has complicated the use of micro-autoradiography. Receptor micro-autoradiography has overcome these complications and is a method of choice. It has been validated through several diffusible compounds with known localization, extensively applied. It has contributed numerous discoveries, followed by new concepts and therapies. Pictorial evidence in this review indicates that cellular information is essential, a 'sine qua non' for meaningful drug distribution studies. High resolution cellular microscopic information obtained from autoradiography requires tissue dissection and the necessary precautions for preserving pristine in vivo drug deposition. Receptor micro-autoradiography fulfils these requirements. It reveals crucial information at the subcellular level that cannot currently be obtained with any other type of autoradiography or spectrometric imaging.
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Affiliation(s)
- Walter E Stumpf
- University of North Carolina at Chapel Hill, 2612 Damascus Church Road, Chapel Hill, NC 27516 USA.
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Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-Ardekani A. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy. Gynecol Endocrinol 2013; 29:396-9. [PMID: 23350644 DOI: 10.3109/09513590.2012.752456] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Low serum vitamin D levels are correlated with insulin resistance during pregnancy. We have assessed the effects of different doses of vitamin D on insulin resistance during pregnancy. A randomized clinical trial was done on 120 women with a gestational age of less than 12 weeks. The women were divided into three groups randomly. Group A received 200 IU vitamin D daily, group B 50,000 IU vitamin D monthly and group C 50,000 IU vitamin D every 2 weeks from 12 weeks of pregnancy until delivery. The serum levels of fasting blood sugar (FBS), insulin, calcium and 25-hydroxyvitamin D were measured before and after intervention. We used the homeostatic model assessment of insulin resistance (HOMA-IR) as a surrogate measure of insulin resistance. The mean ± standard deviation of serum 25-hydroxyvitamin D increased in group C from 7.3 ± 5.9 to 34.1 ± 11.5 ng/ml and in group B it increased from 7.3 ± 5.3 to 27.23 ± 10.7 ng/ml, but the level of vitamin D in group A increased from 8.3 ± 7.8 to 17.7 ± 9.3 ng/ml (p < 0.001). The mean differences of insulin and HOMA-IR before and after intervention in groups A and C were significant (p = 0.01, p = 0.02). This study has shown that supplementation of pregnant women with 50 000 IU vitamin D every 2 weeks improved insulin resistance significantly.
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Affiliation(s)
- Sedigheh Soheilykhah
- Department of Endocrinology, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Piao XX, Han HM. Relationship between vitamin D and nonalcoholic fatty liver disease. Shijie Huaren Xiaohua Zazhi 2013; 21:766-772. [DOI: 10.11569/wcjd.v21.i9.766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Vitamin D is an important secosteroid hormone with pleiotropic effects, including regulation of cell proliferation, differentiation, apoptosis, and immunomodulation. Recently certain evidence has indicated that insufficiency of vitamin D or vitamin D deficiency is related to nonalcoholic fatty liver disease (NAFLD). Subjects with NAFLD have lower serum vitamin D levels than controls, and low vitamin D levels are closely associated with histologic severity of steatosis, necrosis, inflammation and fibrosis in NAFLD. Vitamin D-deficient diet aggravated high fat diet-induced hepatic inflammation in NAFLD models, while vitamin D supplementation improved hepatic histopathology. Vitamin D may act as a regulator in NAFLD through activating VDR and controlling various genes. Modulating hepatic stellate cells is an important mechanism underlying the antifibrotic effect of vitamin D in NAFLD. Vitamin D is a potential drug for treatment for NAFLD, and further prospective RCT studies are required to acquire sufficient evidence.
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Abstract
OBJECTIVE The association of hypovitaminosis D with type 2 diabetes is well recognized. Although hypovitaminosis D is associated with insulin resistance, there is much less information about its impact on β-cell function in humans. METHODS We enrolled 150 healthy, glucose-tolerant subjects for the assessment of β-cell function (acute insulin response) and insulin sensitivity index (ISI) using a hyperglycemic clamp. Adjusted β-cell function (ABCF) was defined as the product of acute insulin response and ISI. The relations of plasma 25-hydroxyvitamin D [25(OH)D] level with insulin sensitivity and ABCF were examined. RESULTS Plasma 25(OH)D levels were positively associated with ABCF (P = 0.00004) and ISI (P < 0.00001). The associations remained significant after adjustment for age, sex, body mass index, physical activity, ethnicity, and season of study. CONCLUSIONS Plasma 25(OH)D levels are positively association with both β-cell function and insulin sensitivity. Our observations suggest the roles of vitamin D deficiency in the dual defect of type 2 diabetes.
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Affiliation(s)
- Rudruidee Karnchanasorn
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, USA
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Where is the vitamin D receptor? Arch Biochem Biophys 2012; 523:123-33. [PMID: 22503810 DOI: 10.1016/j.abb.2012.04.001] [Citation(s) in RCA: 447] [Impact Index Per Article: 34.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Revised: 03/30/2012] [Accepted: 04/01/2012] [Indexed: 02/08/2023]
Abstract
The vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and plays a central role in the biological actions of vitamin D. VDR regulates the expression of numerous genes involved in calcium/phosphate homeostasis, cellular proliferation and differentiation, and immune response, largely in a ligand-dependent manner. To understand the global function of the vitamin D system in physiopathological processes, great effort has been devoted to the detection of VDR in various tissues and cells, many of which have been identified as vitamin D targets. This review focuses on the tissue- and cell type-specific distribution of VDR throughout the body.
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Nephrolithiasis and Its Interrelationship with Vitamin D, Parathyroid Hormone, and Calcium. Urolithiasis 2012. [DOI: 10.1007/978-1-4471-4387-1_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Mathieu C. Vitamin D and diabetes: its importance for beta cell and immune function. Mol Cell Endocrinol 2011; 347:106-20. [PMID: 21889571 DOI: 10.1016/j.mce.2011.08.016] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2011] [Revised: 08/08/2011] [Accepted: 08/12/2011] [Indexed: 02/06/2023]
Abstract
Experimental evidence indicates that vitamin D may play a role in the defense against type 1 diabetes (T1D) as well as type 2 diabetes (T2D). Epidemiological data have established a link between vitamin D deficiency and an increased incidence of both T1D and T2D, whereas early and long-term vitamin D supplementation may decrease the risk of these disorders. The protective effects of vitamin D are mediated through the regulation of several components such as the immune system and calcium homeostasis. However, an increasing amount of evidence suggests that vitamin D also affects beta cells directly thereby rendering them more resistant to the types of cellular stress encountered during T1D and T2D. This review evaluates the role of vitamin D signaling in the pathogenesis of T1D and T2D with a special emphasis on the direct effects of vitamin D on pancreatic beta cells.
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Affiliation(s)
- Heidi Wolden-Kirk
- Laboratory of Experimental Medicine and Endocrinology, University Hospital Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium.
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Abstract
Vitamin D has been produced by plants and animals almost from the time life began. The ability to transport and metabolize vitamin D to more active forms evolved as the structures of plants and animals became more complex, and the cells within these organisms took on more specialized functions. In higher-order animals, the vitamin D receptor (VDR) is found in nearly every cell, and the ability of the cell to produce the active hormone, 1,25(OH)2D, is also widely distributed. Furthermore, the physiological functions with which vitamin D signalling is now associated are as diverse as the tissues in which the VDR is located. Why is this, and is there a common theme? This viewpoint article argues that there is. All cells maintain a fairly constant and submicromolar concentration of free calcium. Calcium is an important regulator of many processes within the cell. The ebb and flow of calcium within cells is controlled by calcium pumps, antiporters and channels. Animals with calcified exo- or endoskeletons have an additional need for calcium, a need that changes during the life cycle of the organism. In this article, I make the case that vitamin D signalling evolved to enable the organism to effectively regulate calcium flux, storage and signalling and that such regulation is critical for the evolutionary process.
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Affiliation(s)
- Daniel D Bikle
- San Francisco Veterans Affairs Medical Center, University of California at San Francisco, CA, USA.
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Abstract
The discovery of the vitamin D endocrine system and a receptor for the hormonal form, 1α,25-dihydroxyvitamin D(3), has brought a new understanding of the relationship between vitamin D and metabolic bone diseases, and has also established the functions of vitamin D beyond the skeleton. This has ushered in many investigations into the possible roles of vitamin D in autoimmune diseases, cardiovascular disorders, infectious diseases, cancers and granuloma-forming diseases. This article presents an evaluation of the possible roles of vitamin D in these diseases. The potential of vitamin D-based therapies in treating diseases for which the evidence is most compelling is also discussed.
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Affiliation(s)
- Lori A Plum
- Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706-1544, USA
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de Jongh RT, Lips P, Rijs KJ, van Schoor NM, Kramer MHH, Vandenbroucke JP, Dekkers OM. Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals. Eur J Endocrinol 2011; 164:75-82. [PMID: 21051524 DOI: 10.1530/eje-10-0688] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
CONTEXT Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality. OBJECTIVE To investigate the associations between VDR gene variants and mortality among older people. DESIGN The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (≥65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms. RESULTS During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2-GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copies=reference, HR, 95% CI: 1 copy 2.01, 0.99-4.07 and 2 copies 1.81, 0.87-4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2-GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83-1.41). CONCLUSIONS The Cdx2-GATA haplotype 1 allele was related to increased mortality risk, which may be partly explained by osteoporotic fractures. As the biological mechanism is uncertain and this study size is limited, our results should be interpreted as hypothesis generating.
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Affiliation(s)
- Renate T de Jongh
- Department of Internal Medicine and Endocrinology EMGO Institute for Health and Care Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
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Delvin EE, Lambert M, Levy E, O'Loughlin J, Mark S, Gray-Donald K, Paradis G. Vitamin D status is modestly associated with glycemia and indicators of lipid metabolism in French-Canadian children and adolescents. J Nutr 2010; 140:987-91. [PMID: 20237070 DOI: 10.3945/jn.109.112250] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
In addition to its recognized role in bone health, recent studies point to vitamin D functions in other tissues, including the pancreas. We tested the association between the vitamin D status and glucose and lipid homeostasis in a school-based, cross-sectional survey of a representative sample of youth. We measured fasting plasma insulin, glucose, total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) apolipoproteins (apo) A1 and B, and 25-hydroxyvitamin D [25(OH)D] concentrations in 878 boys and 867 girls. The 25(OH)D concentrations (mean +/- SD) were 45.9 +/- 12.2 nmol/L in boys and 45.9 +/- 13.0 nmol/L in girls. More than 93% of youth had suboptimal (<75 nmol/L) vitamin D concentrations. There was a slightly lower glycemia, -0.5% (P = 0.015) and -0.4% (P = 0.025), and homeostasis model assessment of insulin resistance, -2.8% (P = 0.043) and -2.3% (P = 0.050), for each 10-nmol/L increase in plasma 25(OH)D in boys and girls, respectively. In contrast, in girls only there were modest increases in plasma TC (1.1%; P = 0.017), TG (2.9%; P = 0.004), apoA1 (1.2%; P < 0.001), and apoB (1.5%; P = 0.023). We observed no association between the presence of at least 2 cardiometabolic risk factors (borderline/unfavorable fasting concentrations of apoB, HDL-C, TG, insulin, and glucose) and 25(OH)D concentrations in either boys or girls. Although the observed associations between 25(OH)D concentrations and fasting glucose, and variables of lipid metabolism are modest, they may have a potential long-term impact on cardiovascular risk.
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Affiliation(s)
- Edgard E Delvin
- Department of Clinical Biochemistry, CHU Sainte-Justine, Montreal, Canada.
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Patel P, Poretsky L, Liao E. Lack of effect of subtherapeutic vitamin D treatment on glycemic and lipid parameters in Type 2 diabetes: A pilot prospective randomized trial. J Diabetes 2010; 2:36-40. [PMID: 20923473 DOI: 10.1111/j.1753-0407.2009.00057.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Epidemiological studies suggest a higher prevalence of metabolic syndrome and its components among individuals with vitamin D deficiency. The aim of the present study was to determine whether vitamin D treatment improves glucose control and insulin sensitivity in Type 2 diabetes mellitus (T2DM). METHODS Subjects with T2DM and serum 25-hydroxyvitamin D (25(OH)D) concentrations <25 ng/mL were randomized to receive 400 IU (Group 1) or 1200 IU (Group 2) cholecalciferol for 4 months. Fasting plasma glucose, glycosylated hemoglobin (HbA1c), Quantitative Insulin Sensitivity Check Index (QUICKI), serum lipid levels and serum adiponectin were measured at baseline and at 4 months. RESULTS Mean 25(OH)D levels increased in both groups (from 17.6±1.5 to 25.5±1.8 ng/mL in Group 1 and from 15.6±1.4 to 27.4±2.4 ng/mL in Group 2; P≤0.001 vs baseline for each group). No significant differences were noted in fasting plasma glucose, HbA1c, QUICKI, serum adiponectin, and lipid levels compared with baseline within groups or between the two groups. CONCLUSIONS In the present pilot study, conventional vitamin D treatment at a level improving, but not optimizing, serum 25(OH)D did not improve glycemia, insulin sensitivity, or lipid profile. However, diabetes and lipids were relatively well controlled at baseline. Future studies should be designed to achieve optimal concentrations of serum 25(OH)D (at least >32 ng/mL) and should include subjects showing more abnormal parameters of glycemia, lipid, and insulin sensitivity at baseline.
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Affiliation(s)
- Parini Patel
- Division of Endocrinology and Friedman Diabetes Institute, Department of Medicine, Beth Israel Medical Center, New York, New York, USA
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31
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Abstract
OBJECTIVE To review the role of vitamin D deficiency for both classic and "nonclassic" effects and raise the caution that association does not prove causation. METHODS The pertinent literature regarding vitamin D and its effects on bone, muscle function, immune function, glucose tolerance, cancer risk, and development of cardiovascular disease and other conditions is reviewed. In addition, the limitations of observational studies are discussed. RESULTS Vitamin D inadequacy is common worldwide and classically causes osteomalacia and rickets. More recently, the contribution of low vitamin D status to increased falls and fracture risk has become appreciated. Additionally, nonclassic effects of vitamin D inadequacy are being recognized, and low vitamin D status is being potentially associated with a multitude of conditions (including Alzheimer disease, osteoarthritis, multiple sclerosis, and hypertension) and higher overall mortality. It is important to recognize that associations in observational studies can be due to chance, bias, or confounders or may be indicative of causality. CONCLUSION Because vitamin D deficiency has been established to have adverse musculoskeletal consequences, optimization of vitamin D status, for both the individual patient and the overall population, is indicated.
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Affiliation(s)
- Neil Binkley
- University of Wisconsin Osteoporosis Research, 2870 University Avenue, Suite 100, Madison, WI 53705, USA.
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Farrant HJW, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, Osmond C, Veena SR, Fall CHD. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J Clin Nutr 2009; 63:646-52. [PMID: 18285809 PMCID: PMC2678985 DOI: 10.1038/ejcn.2008.14] [Citation(s) in RCA: 174] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2007] [Revised: 01/10/2008] [Accepted: 01/10/2008] [Indexed: 11/08/2022]
Abstract
BACKGROUND/OBJECTIVES Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We have related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population. SUBJECTS/METHODS Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies' anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured. RESULTS In total 66% of women had hypovitaminosis D (25(OH)D concentrations <50 nmol l(-1)) and 31% were below 28 nmol l(-1). There was seasonal variation in 25(OH)D concentrations (P<0.0001). There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D). Maternal 25(OH)D concentrations were unrelated to newborn anthropometry or cord plasma variables. In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04). CONCLUSIONS Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth or altered neonatal cord plasma insulin secretory profile.
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Affiliation(s)
- Hannah JW Farrant
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD
| | | | - Jacqueline C Hill
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD
| | - Barbara J Boucher
- Centre for Diabetes and Metabolic Medicine, Institute for Cellular and Molecular Science, Barts and the London School of Medicine and Dentistry, London, E1 2AT
| | - David J Fisher
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD
| | - Kate Noonan
- Department of Clinical Biochemistry, Barts and the London NHS Trust, London, E1 2AD
| | - Clive Osmond
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD
| | | | - Caroline HD Fall
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD
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35
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Abstract
CONTEXT Vitamin D receptors are found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. These nonclassic tissues are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)(2)D. Furthermore, many of these tissues also contain the enzyme CYP27B1 capable of producing 1,25(OH)(2)D from the circulating form of vitamin D. This review was intended to highlight the actions of 1,25(OH)(2)D in several of these tissues but starts with a review of vitamin D production, metabolism, and molecular mechanism. EVIDENCE ACQUISITION Medline was searched for articles describing actions of 1,25(OH)(2)D on parathyroid hormone and insulin secretion, immune responses, keratinocytes, and cancer. EVIDENCE SYNTHESIS Vitamin D production in the skin provides an efficient source of vitamin D. Subsequent metabolism to 1,25(OH)(2)D within nonrenal tissues differs from that in the kidney. Although vitamin D receptor mediates the actions of 1,25(OH)(2)D, regulation of transcriptional activity is cell specific. 1,25(OH)(2)D inhibits PTH secretion but promotes insulin secretion, inhibits adaptive immunity but promotes innate immunity, and inhibits cell proliferation but stimulates their differentiation. CONCLUSIONS The nonclassic actions of vitamin D are cell specific and provide a number of potential new clinical applications for 1,25(OH)(2)D(3) and its analogs. However, the use of vitamin D metabolites and analogs for these applications remains limited by the classic actions of vitamin D leading to hypercalcemia and hypercalcuria.
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Affiliation(s)
- Daniel Bikle
- Veterans Affairs Medical Center (111N), 4150 Clement Street, San Francisco, California 94121, USA.
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36
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37
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Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei AR, Larijani B. Correlation between vitamin D3 deficiency and insulin resistance in pregnancy. Diabetes Metab Res Rev 2008; 24:27-32. [PMID: 17607661 DOI: 10.1002/dmrr.737] [Citation(s) in RCA: 184] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The serum level of 25-hydroxyvitamin D deficiency has long been suspected as a risk factor for glucose intolerance and perhaps 1,25-dihydroxyvitamin D has a role in the regulation of insulin secretion. This study investigates the relation between 25-hydroxyvitamin D concentrations and insulin resistance in pregnant women. METHODS A cross-sectional study was conducted on 741 pregnant women referred to five educating hospital clinics. Universal screening was performed with a GCT-50 g, and those with plasma glucose levels > pr = 7.2 mmol/L were diagnosed as GDM if they had an impaired GTT-100 g based on Carpenter and Coustan criteria. The levels of insulin and C-peptide were measured during OGTT-100 g test. The homeostasis model assessment index (HOMA) equation was used as the insulin resistance index. The concentrations of 25-hydroxyvitamin D, and PTH were also measured. RESULTS Total prevalence of vitamin D deficiency (<25 nmol/L) was found in 70.6% of pregnant women. Prevalence of severe vitamin D deficiency (<12.5) in GDM patients was higher than in normoglycaemic pregnancies. The regression model revealed a strong correlation between the HOMA index and serum levels of vitamin D. CONCLUSIONS These results show that a positive correlation of 25(OH) vitamin D concentrations with insulin sensitivity and vitamin D deficiency could be a confirmative sign of insulin resistance.
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Affiliation(s)
- Zhila Maghbooli
- Endocrinology & Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Kamycheva E, Jorde R, Figenschau Y, Haug E. Insulin sensitivity in subjects with secondary hyperparathyroidism and the effect of a low serum 25-hydroxyvitamin D level on insulin sensitivity. J Endocrinol Invest 2007; 30:126-32. [PMID: 17392602 DOI: 10.1007/bf03347410] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
To investigate the relation between secondary hyperparathyroidism (SHPT) and insulin sensitivity, 15 subjects with SHPT (serum PTH >6.4 pmol/l, serum calcium <2.40 mmol/l, and normal serum creatinine) and 15 control subjects were investigated with an oral glucose tolerance test (OGTT) and a 3-h hyperglycemic clamp. Body composition was measured with dual-energy X-ray absorptiometry. No differences were found between the SHPT and control groups on any indices of glucose or insulin metabolism. However, when dividing the 30 subjects in the upper and lower halves according to serum 25-hydroxyvitamin D levels (<59 and >58 nmol/l), those in the lower half had significantly higher 2-h serum insulin value at the OGTT, significantly higher insulin secretion during the last hour of the clamp, and significantly lower insulin sensitivity index (ISI; glucose infusion rate/insulin secretion during the last hour of the clamp). In a multiple linear regression analysis correcting for age, gender, and body mass index (BMI), the serum 25-hydroxyvitamin D level was significantly and positively associated with the ISI. The amounts of total body and truncal fat were negatively and significantly associated with the ISI, whereas no association between measures of lean body mass were associated with insulin secretion or sensitivity.
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Affiliation(s)
- E Kamycheva
- Department of Medicine, University Hospital of North Norway, Tromsø, Norway.
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39
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Abstract
Ca(2+) is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function. The Ca(2+) balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on average 1 g Ca(2+) daily from which 0.35 g is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca(2+) balance, the kidney must excrete the same amount of Ca(2+) that the small intestine absorbs. This is accomplished by a combination of filtration of Ca(2+) across the glomeruli and subsequent reabsorption of the filtered Ca(2+) along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca(2+) fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D(3)) and parathyroid hormone. Until recently, the mechanism by which Ca(2+) enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca(2+) channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca(2+) channels constitute the rate-limiting step in Ca(2+)-transporting epithelia. They form the prime target for hormonal control of the active Ca(2+) flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca(2+) transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca(2+) channels accumulating in a comprehensive model for epithelial Ca(2+) absorption.
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Affiliation(s)
- Joost G J Hoenderop
- Department of Physiology, Nijmegen Center for Moecular Life Sciences, University Medical Center Nijmegen, The Netherlands
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Janssen SWJ, Hoenderop JGJ, Hermus ARMM, Sweep FCGJ, Martens GJM, Bindels RJM. Expression of the novel epithelial Ca2+ channel ECaC1 in rat pancreatic islets. J Histochem Cytochem 2002; 50:789-98. [PMID: 12019295 DOI: 10.1177/002215540205000605] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The epithelial Ca2+ channel, ECaC1, is primarily expressed in the apical membrane of vitamin D-responsive tissues. This study characterizes for the first time the presence of this novel channel in pancreatic tissue by reverse transcriptase-polymerase chain reaction and immunohistochemistry. In addition, the expression of ECaC1 was investigated in an animal model for Type 2 diabetes mellitus, the Zucker diabetic fatty (ZDF) rat. Identical staining patterns for ECaC1 and insulin were observed, whereas no co-localization of ECaC1 with glucagon was found. ECaC1, insulin, and prohormone convertase 1 (a neuroendocrine endoprotease expressed in secretory granules) showed a similar punctate staining. ECaC1 co-localized with the Ca2+ binding protein calbindin-D(28K) in the beta-cells. Furthermore, in contrast to wild-type rats, in ZDF rats aging led to a progressive decrease in both insulin and ECaC1 staining. Plasma 1,25-dihydroxyvitamin D3 levels were similar in both control and ZDF rats and decreased with aging. Taken together, our findings indicate that this novel Ca2+ channel may play a role in the regulation of endocrine Ca2+ homeostasis.
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Affiliation(s)
- Susan W J Janssen
- Department of Animal Physiology, Faculty of Science, University of Nijmegen, Nijmegen, The Netherlands
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Sooy K, Schermerhorn T, Noda M, Surana M, Rhoten WB, Meyer M, Fleischer N, Sharp GW, Christakos S. Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem 1999; 274:34343-9. [PMID: 10567411 DOI: 10.1074/jbc.274.48.34343] [Citation(s) in RCA: 75] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The role of the calcium-binding protein, calbindin-D(28k) in potassium/depolarization-stimulated increases in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release was investigated in pancreatic islets from calbindin-D(28k) nullmutant mice (knockouts; KO) or wild type mice and beta cell lines stably transfected and overexpressing calbindin. Using single islets from KO mice and stimulation with 45 mM KCl, the peak of [Ca(2+)](i) was 3.5-fold greater in islets from KO mice compared with wild type islets (p < 0.01) and [Ca(2+)](i) remained higher during the plateau phase. In addition to the increase in [Ca(2+)](i) in response to KCl there was also a significant increase in insulin release in islets isolated from KO mice. Evidence for modulation by calbindin of [Ca(2+)](i) and insulin release was also noted using beta cell lines. Rat calbindin was stably expressed in betaTC-3 and betaHC-13 cells. In response to depolarizing concentrations of K(+), insulin release was decreased by 45-47% in calbindin expressing betaTC cells and was decreased by 70-80% in calbindin expressing betaHC cells compared with insulin release from vector transfected betaTC or betaHC cells (p < 0.01). In addition, the K(+)-stimulated intracellular calcium peak was markedly inhibited in calbindin expressing betaHC cells compared with vector transfected cells (225 nM versus 1,100 nM, respectively). Buffering of the depolarization-induced rise in [Ca(2+)](i) was also observed in calbindin expressing betaTC cells. In summary, our findings, using both isolated islets from calbindin-D(28k) KO mice and beta cell lines, establish a role for calbindin in the modulation of depolarization-stimulated insulin release and suggest that calbindin can control the rate of insulin release via regulation of [Ca(2+)](i).
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Affiliation(s)
- K Sooy
- Department of Biochemistry, University of Medicine and Dentistry of New Jersey, New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, New Jersey 07103, USA
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Kajikawa M, Ishida H, Fujimoto S, Mukai E, Nishimura M, Fujita J, Tsuura Y, Okamoto Y, Norman AW, Seino Y. An insulinotropic effect of vitamin D analog with increasing intracellular Ca2+ concentration in pancreatic beta-cells through nongenomic signal transduction. Endocrinology 1999; 140:4706-12. [PMID: 10499529 DOI: 10.1210/endo.140.10.7025] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The effect of 1alpha,25-dihydroxylumisterol3 (1alpha,25(OH)2lumisterol3) on insulin release from rat pancreatic beta-cells was measured to investigate the nongenomic action of vitamin D via the putative membrane vitamin D receptor (mVDR). 1Alpha,25(OH)2lumisterol3, a specific agonist of mVDR, dose-dependently augmented 16.7 mM glucose-induced insulin release from rat pancreatic islets and increased the intracellular Ca2+ concentration ([Ca2+]i), though not increasing Ca2+ efficacy in the exocytotic system. These effects were completely abolished by an antagonist of mVDR, 1beta,25-dihydroxyvitamin D3 (1beta,25(OH)2D3), or by a blocker of voltage-dependent Ca2+ channels, nitrendipine. Moreover, both [Ca2+]i elevation, caused by membrane depolarization, and sufficient intracellular glucose metabolism are required for the expression of these effects. 1Alpha,25(OH)2lumisterol3, therefore, has a rapid insulinotropic effect, through nongenomic signal transduction via mVDR, that would be dependent on the augmentation of Ca2+ influx through voltage-dependent Ca2+ channels on the plasma membrane, being also linked to metabolic signals derived from glucose in pancreatic beta-cells. However, further investigations will be needed to discuss physiologically the meaning of insulinotropic effects of vitamin D through mVDR.
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Affiliation(s)
- M Kajikawa
- Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
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Stumpf WE. Receptor localization of steroid hormones and drugs: discoveries through the use of thaw-mount and dry-mount autoradiography. Braz J Med Biol Res 1998; 31:197-206. [PMID: 9686142 DOI: 10.1590/s0100-879x1998000200003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The history of receptor autoradiography, its development and applications, testify to the utility of this histochemical technique for localizing radiolabeled hormones and drugs at cellular and subcellular sites of action in intact tissues. Localization of diffusible compounds has been a challenge that was met through the introduction of the "thaw-mount" and "dry-mount" autoradiographic techniques thirty years ago. With this cellular receptor autoradiography, used alone or combined with other histochemical techniques, sites of specific binding and deposition in vivo and in vitro have been characterized. Numerous discoveries, some reviewed in this article, provided information that led to new concepts and opened new areas of research. As an example, in recent years more than fifty target tissues for vitamin D have been specified, challenging the conventional view about the main biological role of vitamin D. The functions of most of these vitamin D target tissues are unrelated to the regulation of systemic calcium homeostasis, but pertain to the (seasonal) regulation of endo- and exocrine secretion, cell proliferation, reproduction, neural, immune and cardiovascular responses, and adaptation to stress. Receptor autoradiography with cellular resolution has become an indispensable tool in drug research and development, since information can be obtained that is difficult or impossible to gain otherwise.
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Affiliation(s)
- W E Stumpf
- University of North Carolina at Chapel Hill, USA.
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Bourlon PM, Faure-Dussert A, Billaudel B. Modulatory role of 1,25 dihydroxyvitamin D3 on pancreatic islet insulin release via the cyclic AMP pathway in the rat. Br J Pharmacol 1997; 121:751-8. [PMID: 9208144 PMCID: PMC1564753 DOI: 10.1038/sj.bjp.0701204] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
1. Previous studies have shown that vitamin D3 deficiency impairs the insulin response to glucose via an alteration of signal transduction pathways, such as Ca2+ handling and the phosphoinositide pathway. In the present study the adenylyl cyclase pathway was examined in islets from 3 independent groups: normal rats, 4 weeks-vitamin D3 deficient rats and one week-1,25 dihydroxyvitamin D3 (1,25(OH)2D3) treated rats. 2. We found that the very low rate of insulin release observed in vitamin D3 deficient rats could be restored in vitamin D3 deficient islets only with high concentrations of dioctanoyl-cyclic AMP (DO-cyclic AMP), whereas 1,25(OH)2D3 improved the sensitivity of the islets to this exogenous cyclic AMP analogue. 3. The beneficial effect of 1,25(OH)2D3 observed with or without DO-cyclic AMP was protein kinase A-dependent, since the addition of N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulphonamide (H-89), a specific inhibitor of cyclic AMP-dependent protein kinases, decreased the insulin release of treated rats back to the level seen in vitamin D3 deficient islets. 4. The low rate of insulin release could not be consistently related to an alteration in cyclic AMP content of the islets. Indeed, low insulin response to a barium+theophylline stimulus observed in vitamin D3 deficient islets was paradoxically associated with a supranormal cyclic AMP content in the islets. 5. This paradoxical increase in cyclic AMP observed in these conditions could not be attributed to a lower total phosphodiesterase (PDE) activity, although the portion of Ca(2+)-calmodulin-independent PDE was predominant in islets from vitamin D3 deficient rats. 6. On the other hand, the higher cyclic AMP content of vitamin D3 deficient islets could be related to an increase in glucagon-induced cyclic AMP synthesis in relation to the hyperglucagonaemia previously observed in vitamin D3 deficient rats. Since higher concentrations of exogenous glucagon and higher endogenous cyclic AMP concentrations were required in vitro to restore insulin release to normal values, the cyclic AMP-dependent pathways that usually potentiate insulin secretion appeared to be less efficient in relation to an alteration in the post cyclic AMP effector system. 7. 1,25(OH)2D3 exerted a stimulating effect on insulin release via protein kinase A activation but reduced the supranormal cyclic AMP synthesis, thus exerting a differential modulatory influence on biochemical disturbances in islets induced by vitamin D3 deficiency.
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Affiliation(s)
- P M Bourlon
- Laboratoire d'Endocrinologie, Université de Bordeaux 1, Talence Cedex, France
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Reddy D, Pollock AS, Clark SA, Sooy K, Vasavada RC, Stewart AF, Honeyman T, Christakos S. Transfection and overexpression of the calcium binding protein calbindin-D28k results in a stimulatory effect on insulin synthesis in a rat beta cell line (RIN 1046-38). Proc Natl Acad Sci U S A 1997; 94:1961-6. [PMID: 9050887 PMCID: PMC20025 DOI: 10.1073/pnas.94.5.1961] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/1996] [Accepted: 12/16/1996] [Indexed: 02/03/2023] Open
Abstract
Calbindin-D28k, a calcium binding protein that is thought to act as a facilitator of calcium diffusion in intestine and kidney, is known to be regulated by vitamin D in these tissues. Calbindin-D28k is also present in pancreatic beta cells, but its function in these cells is not known. To determine a role for calbindin-D28k in the beta cell, rat calbindin-D28k was overexpressed in the pancreatic beta cell line RIN 1046-38 by transfection of calbindin in expression vector, and changes in insulin mRNA were examined. Five transfected RIN cell clones were found to overexpress calbindin 6- to 35-fold as determined by radioimmunoassay. Northern blot analysis revealed increases in abundance in calbindin mRNA (>20-fold for most clones). Overexpressed calbindin was functional because it was capable of buffering calcium in response to a rapid calcium influx induced by 1 and 5 microM calcium ionophore. In cells transfected with calbindin, there was a marked increase in the expression of insulin mRNA (>20-fold for most clones compared with vector transfected cells). Besides an increase in insulin mRNA, calbindin overexpression was also associated with an increase in insulin content and release (a 5.8-fold increase in insulin release was noted for clone C10, and a 54-fold increase was noted for clone C2). To begin to address the mechanism whereby overexpression of calbindin results in increased insulin gene expression, calbindin-overexpressing clones were transiently transfected with plasmids incorporating various regions of the rat insulin I (rInsI) promoter linked to the chloramphenicol acetyltransferase coding sequence. Transient transfection with reporter plasmids bearing the regulatory sequences of the rInsI promoter (-345/+1) or five copies of the Far-FLAT minienhancer (-247/-198) from the rInsI promoter suggests that increased insulin mRNA in calbindin transfected cells is due, at least in part, to enhanced insulin gene transcription. These studies provide the first direct evidence (to our knowledge) for a role for calbindin in beta cell function.
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Affiliation(s)
- D Reddy
- Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA
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Stumpf WE. Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting. Histochem Cell Biol 1995; 104:417-27. [PMID: 8777727 DOI: 10.1007/bf01464331] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Knowledge about sites and mechanisms of action of vitamin D and its analogs has been greatly advanced by histochemical approaches. High resolution and high sensitivity, combined with the integrative potential of relatively intact histochemical tissue preparations, contributed information that is difficult or impossible to obtain otherwise. In in vivo distribution studies with conventional biochemical assays, target cell populations associated with non-target tissues frequently remain unrecognized without the resolution achieved by cellular autoradiography. Autoradiography, alone or combined with immunohistochemistry when applied to in vivo drug targeting and target characterization, has provided information on cellular-subcellular receptor distribution in over 50 tissues. These discoveries, importantly, contribute to a new understanding of the biological role of vitamin D and challenge the concept of "the calcium homeostatic steroid hormone" as being too narrow. While some of the outstanding effects of vitamin D deficiency and toxicity relate to calcium homeostasis, the vast majority of the target tissues appear not to be primarily related to calcium metabolism, but rather to the activation and regulation of exo- and endocrine secretory and somatotrophic processes such as cell differentiation and proliferation. Also, several highly calcium-dependent tissues such as striated and smooth muscles are not genomic targets for vitamin D. The reviewed data on the diverse and extensive presence of target tissues forecast a high therapeutic potential for vitamin D and especially its low-calcemic analogs, far beyond that which is presently utilized. The evidence provided for vitamin D also testifies to the utility and need to include in vivo cytopharmacology in any target evaluation of bioactive compounds to further the understanding of their mechanisms of action, and to identify preferential targets and their differential therapeutic and toxic potentials.
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Affiliation(s)
- W E Stumpf
- International Institute of Drug Distribution, Chapel Hill, NC 27516, USA
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Sandler S, Buschard K, Bendtzen K. Effects of 1,25-dihydroxyvitamin D3 and the analogues MC903 and KH1060 on interleukin-1 beta-induced inhibition of rat pancreatic islet beta-cell function in vitro. Immunol Lett 1994; 41:73-7. [PMID: 7959906 DOI: 10.1016/0165-2478(94)90059-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The cytokine interleukin-1 beta (IL-1 beta) has been proposed to be involved in pancreatic beta-cell destruction during the development of autoimmune insulin-dependent diabetes mellitus. It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits T-lymphocyte and monocyte functions in vitro, probably through an effect on cytokine actions, and that in vivo treatment with vitamin D can prevent pancreatic insulitis in diabetes-prone NOD mice. In this study isolated rat pancreatic islets were exposed to human IL-1 beta (25 U/ml) in the absence or presence of 1,25-(OH)2D3 or the analogues MC903 and KH1060 for 48-72 h in tissue culture, whereupon medium insulin accumulation, islet DNA and insulin contents, glucose-stimulated insulin secretion and glucose oxidation rates were assessed. All three vitamin D derivatives counteracted the suppressive effect of IL-1 beta on medium insulin accumulation, 1,25-(OH)2D3 being active at concentrations down to 0.1 nM, i.e., 1-2 orders of magnitude more efficacious than the analogues. However, only KH1060 opposed the suppressive effect of IL-1 beta on islet glucose-stimulated insulin secretion and glucose oxidation rate despite the fact that KH1060 itself reduced the islet DNA and insulin content by approximately 10% and 30%, respectively. The protective effect observed against IL-1 beta-induced beta-cell dysfunction might be related to a beneficial action of vitamin D3 on the mitochondrial calcium metabolism of the beta-cells.
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Affiliation(s)
- S Sandler
- Department of Medical Cell Biology, Uppsala University, Sweden
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Affiliation(s)
- T K Ross
- Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706
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Schleicher G, Bartke A, Bidmon HJ, Stumpf WE. 1,25(OH)2 vitamin D3 binding sites in male sex organs of the Siberian hamster (Phodopus sungorus). An autoradiographic study. J Steroid Biochem Mol Biol 1993; 46:331-5. [PMID: 9831481 DOI: 10.1016/0960-0760(93)90222-i] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Using autoradiography, binding sites for 1,25(OH)2 vitamin D3 are found in certain genital organs of male Siberian hamsters (Phodopus sungorus), in particular in basal epithelial cells and fibroblasts of the lamina propria of prostate glands. Scattered labeled cells are also present in the epithelium of coagulation and urethral glands. In contrast to the findings in mice, under the conditions of the experiment, 1,25(OH)2 vitamin D3 binding sites are not recognizable in other accessory sex glands and gonads. The frequency of basal epithelial cells with [3H]1,25(OH)2 vitamin D3 nuclear binding is higher in regressed dorsal prostate glands of animals living in short photoperiods. The data suggest that 1,25(OH)2 vitamin D3 may promote proliferation and differentiation in basal epithelial cells, modulated by the seasonal and functional status of the animal.
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Affiliation(s)
- G Schleicher
- Universität (GHS) Essen, Abteilung für Pädiatrische Endokrinologie, Zentrum für Kinder- und Jugendmedizin, Germany
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Stumpf WE, Pérez-Delgado MM, Li L, Bidmon HJ, Tuohimaa P. Vitamin D3 (soltriol) nuclear receptors in abdominal scent gland and skin of Siberian hamster (Phodopus sungorus) localized by autoradiography and immunohistochemistry. HISTOCHEMISTRY 1993; 100:115-9. [PMID: 8244763 DOI: 10.1007/bf00572897] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
In vivo autoradiography with [3H]1,25-dihydroxycholecalciferol (vitamin D, soltriol) and immunostaining with antibodies to vitamin D receptor were applied to identify specific binding sites in the abdominal scent gland of male Siberian hamster (Phodopus sungorus). Nuclear concentration of radiolabeled hormone and receptor antibodies was observed in the corresponding cell types including basal cells of sebaceous glands, cells of the outer hair sheaths and hair bulbs, and also keratinocytes in the epidermis. Cells of the hair dermal papillae and fibroblasts of the dermis did not show nuclear labeling. There was good correspondence between the autoradiographic and immunohistochemical data. The results indicate the presence of receptors for vitamin D-soltriol and suggest a seasonal regulation of scent gland marking activities by this steroid hormone of sunlight in cooperation with the sex steroid testosterone.
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Affiliation(s)
- W E Stumpf
- Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599-7090
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