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Jin C, Chen H, Xie L, Zhou Y, Liu LL, Wu J. GPCRs involved in metabolic diseases: pharmacotherapeutic development updates. Acta Pharmacol Sin 2024; 45:1321-1336. [PMID: 38326623 PMCID: PMC11192902 DOI: 10.1038/s41401-023-01215-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 12/11/2023] [Indexed: 02/09/2024] Open
Abstract
G protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including nutrient synthesis, transportation, storage or insulin sensitivity, etc. This review intends to summarize the regulation of metabolic homeostasis and mechanisms by a series of GPCRs, such as GPR91, GPR55, GPR119, GPR109a, GPR142, GPR40, GPR41, GPR43 and GPR120. With deep understanding of GPCR's structure and signaling pathways, it is attempting to uncover the role of GPCRs in major metabolic diseases, including metabolic syndrome, diabetes, dyslipidemia and nonalcoholic steatohepatitis, for which the global prevalence has risen during last two decades. An extensive list of agonists and antagonists with their chemical structures in a nature of small molecular compounds for above-mentioned GPCRs is provided as pharmacologic candidates, and their preliminary data of preclinical studies are discussed. Moreover, their beneficial effects in correcting abnormalities of metabolic syndrome, diabetes and dyslipidemia are summarized when clinical trials have been undertaken. Thus, accumulating data suggest that these agonists or antagonists might become as new pharmacotherapeutic candidates for the treatment of metabolic diseases.
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Affiliation(s)
- Cheng Jin
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
- College of Clinical Medicine, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Hui Chen
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Li Xie
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Yuan Zhou
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Li-Li Liu
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
| | - Jian Wu
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
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Hryciw DH, Patten RK, Rodgers RJ, Proietto J, Hutchinson DS, McAinch AJ. GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates. Expert Opin Investig Drugs 2024; 33:183-190. [PMID: 38372052 DOI: 10.1080/13543784.2024.2321271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/16/2024] [Indexed: 02/20/2024]
Abstract
INTRODUCTION Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the β-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic. AREAS COVERED This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D. EXPERT OPINION GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.
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Affiliation(s)
- Deanne H Hryciw
- School of Environment and Science, Griffith University, Nathan, Queensland, Australia
- Griffith Institute of Drug Discovery, Griffith University, Nathan, Queensland, Australia
| | - Rhiannon K Patten
- Institute for Health and Sport, Victoria University, Melbourne, Australia
| | - Raymond J Rodgers
- Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Joseph Proietto
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Dana S Hutchinson
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Andrew J McAinch
- Institute for Health and Sport, Victoria University, Melbourne, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, VIC, Australia
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Mingrone G, Castagneto-Gissey L, Bornstein SR. New Horizons: Emerging Antidiabetic Medications. J Clin Endocrinol Metab 2022; 107:e4333-e4340. [PMID: 36106900 DOI: 10.1210/clinem/dgac499] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Indexed: 02/13/2023]
Abstract
Over the past century, since the discovery of insulin, the therapeutic offer for diabetes has grown exponentially, in particular for type 2 diabetes (T2D). However, the drugs in the diabetes pipeline are even more promising because of their impressive antihyperglycemic effects coupled with remarkable weight loss. An ideal medication for T2D should target not only hyperglycemia but also insulin resistance and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the new class of GLP1 and gastric inhibitory polypeptide dual RAs counteract 2 of these metabolic defects of T2D, hyperglycemia and obesity, with stunning results that are similar to the effects of metabolic surgery. An important role of antidiabetic medications is to reduce the risk and improve the outcome of cardiovascular diseases, including coronary artery disease and heart failure with reduced or preserved ejection fraction, as well as diabetic nephropathy, as shown by SGLT2 inhibitors. This review summarizes the main drugs currently under development for the treatment of type 1 diabetes and T2D, highlighting their strengths and side effects.
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Affiliation(s)
- Geltrude Mingrone
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome 00169, Italy
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00169, Italy
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London WC2R 2LS, UK
| | | | - Stefan R Bornstein
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London WC2R 2LS, UK
- Department of Medicine III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden 01307, Germany
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Zhao J, Zhao Y, Hu Y, Peng J. Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease. Cell Mol Biol Lett 2021; 26:32. [PMID: 34233623 PMCID: PMC8265056 DOI: 10.1186/s11658-021-00276-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 07/02/2021] [Indexed: 12/22/2022] Open
Abstract
In the past decade, G protein-coupled receptors have emerged as drug targets, and their physiological and pathological effects have been extensively studied. Among these receptors, GPR119 is expressed in multiple organs, including the liver. It can be activated by a variety of endogenous and exogenous ligands. After GPR119 is activated, the cell secretes a variety of incretins, including glucagon-like peptide-1 and glucagon-like peptide-2, which may attenuate the metabolic dysfunction associated with fatty liver disease, including improving glucose and lipid metabolism, inhibiting inflammation, reducing appetite, and regulating the intestinal microbial system. GPR119 has been a potential therapeutic target for diabetes mellitus type 2 for many years, but its role in metabolic dysfunction associated fatty liver disease deserves further attention. In this review, we discuss relevant research and current progress in the physiology and pharmacology of the GPR119/incretin axis and speculate on the potential therapeutic role of this axis in metabolic dysfunction associated with fatty liver disease, which provides guidance for transforming experimental research into clinical applications.
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Affiliation(s)
- Jianan Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated To Shanghai, University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China
| | - Yu Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated To Shanghai, University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China.,Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Pudong District, Shanghai, 201203, China.,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528, Zhangheng Road, Shanghai, China
| | - Yiyang Hu
- Institute of Clinical Pharmacology, Shuguang Hospital Affiliated To Shanghai, University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China. .,Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Pudong District, Shanghai, 201203, China. .,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528, Zhangheng Road, Shanghai, China.
| | - Jinghua Peng
- Institute of Liver Diseases, Shuguang Hospital Affiliated To Shanghai, University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China. .,Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Pudong District, Shanghai, 201203, China. .,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528, Zhangheng Road, Shanghai, China.
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Manaithiya A, Alam O, Sharma V, Javed Naim M, Mittal S, Khan IA. GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus. Bioorg Chem 2021; 113:104998. [PMID: 34048996 DOI: 10.1016/j.bioorg.2021.104998] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/05/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in β-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependent insulin secretion and glucose-dependent insulinotropic peptide (GIP). In this manuscript, we have reviewed the work done in the last five years (2015-2020) which gives an approach to design, synthesize, evaluate and study the structural activity relationship of novel GPR119 agonist-based lead compounds. Our article would help the researchers and guide their endeavours in the direction of strategy and development of innovative, effective GPR119 agonist-based compounds for the management of diabetes mellitus type 2.
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Affiliation(s)
- Ajay Manaithiya
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Ozair Alam
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India.
| | - Vrinda Sharma
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Mohd Javed Naim
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Shruti Mittal
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Imran A Khan
- Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi-110062, India
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Therapeutic of Candesartan and Music Therapy in Diabetic Retinopathy with Depression in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5570356. [PMID: 33833815 PMCID: PMC8018856 DOI: 10.1155/2021/5570356] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/11/2021] [Accepted: 03/17/2021] [Indexed: 12/31/2022]
Abstract
This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.
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Ghislain J, Poitout V. Targeting lipid GPCRs to treat type 2 diabetes mellitus - progress and challenges. Nat Rev Endocrinol 2021; 17:162-175. [PMID: 33495605 DOI: 10.1038/s41574-020-00459-w] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
Therapeutic approaches to the treatment of type 2 diabetes mellitus that are designed to increase insulin secretion either directly target β-cells or indirectly target gastrointestinal enteroendocrine cells (EECs), which release hormones that modulate insulin secretion (for example, incretins). Given that β-cells and EECs both express a large array of G protein-coupled receptors (GPCRs) that modulate insulin secretion, considerable research and development efforts have been undertaken to design therapeutic drugs targeting these GPCRs. Among them are GPCRs specific for free fatty acid ligands (lipid GPCRs), including free fatty acid receptor 1 (FFA1, otherwise known as GPR40), FFA2 (GPR43), FFA3 (GPR41) and FFA4 (GPR120), as well as the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). These lipid GPCRs have demonstrated important roles in the control of islet and gut hormone secretion. Advances in lipid GPCR pharmacology have led to the identification of a number of synthetic agonists that exert beneficial effects on glucose homeostasis in preclinical studies. Yet, translation of these promising results to the clinic has so far been disappointing. In this Review, we present the physiological roles, pharmacology and clinical studies of these lipid receptors and discuss the challenges associated with their clinical development for the treatment of type 2 diabetes mellitus.
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Affiliation(s)
- Julien Ghislain
- Montreal Diabetes Research Center, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
| | - Vincent Poitout
- Montreal Diabetes Research Center, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
- Department of Medicine, Université de Montréal, Montréal, QC, Canada.
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Yang M, Zhang CY. G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment. World J Gastroenterol 2021; 27:677-691. [PMID: 33716447 PMCID: PMC7934005 DOI: 10.3748/wjg.v27.i8.677] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/24/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a broad-spectrum disease, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis, which can progress to cirrhosis and liver cancer. Abnormal hepatic lipid accumulation is the major manifestation of this disease, and lipotoxicity promotes NAFLD progression. In addition, intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins, resulting in progression of NAFLD to fibrosis and even cirrhosis. G protein-coupled receptors (GPCRs) have been shown to play essential roles in metabolic disorders, such as NAFLD and obesity, through their function as receptors for bile acids and free fatty acids. In addition, GPCRs link gut microbiota-mediated connections in a variety of diseases, such as intestinal diseases, hepatic steatosis, diabetes, and cardiovascular diseases. The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids. GPCR agonists, including peptides and natural products like docosahexaenoic acid, have been applied to investigate their role in liver diseases. Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome. This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment. Overall, understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.
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Affiliation(s)
- Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Chun-Ye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, United States
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Li M, Ding L, Hu YL, Qin LL, Wu Y, Liu W, Wu LL, Liu TH. Herbal formula LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis in Zucker diabetic fatty rats. J Cell Mol Med 2020; 25:367-382. [PMID: 33215869 PMCID: PMC7810939 DOI: 10.1111/jcmm.16084] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 10/21/2020] [Accepted: 10/25/2020] [Indexed: 12/22/2022] Open
Abstract
LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.
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Affiliation(s)
- Mei Li
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Ding
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yu-Li Hu
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ling-Ling Qin
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - You Wu
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Liu
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Li-Li Wu
- Key Laboratory of Health Cultivation of the Ministry of Education, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Tong-Hua Liu
- Key Laboratory of Health Cultivation of the Ministry of Education, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.,Tibetan Medical College, Lhasa, China
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Zeng Z, Huang SY, Sun T. Pharmacogenomic Studies of Current Antidiabetic Agents and Potential New Drug Targets for Precision Medicine of Diabetes. Diabetes Ther 2020; 11:2521-2538. [PMID: 32930968 PMCID: PMC7548012 DOI: 10.1007/s13300-020-00922-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Indexed: 12/29/2022] Open
Abstract
Diabetes is a major threat to people's health and has become a burden worldwide. Current drugs for diabetes have limitations, such as different drug responses among individuals, failure to achieve glycemic control, and adverse effects. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Currently pharmacogenomics has provided potential for individualized drug therapy based on genetic and genomic information of patients, and has made precision medicine possible. Responses and adverse effects to antidiabetic drugs are significantly associated with gene polymorphisms in patients. Many new targets for diabetes also have been discovered and developed, and even entered clinical trial phases. This review summarizes pharmacogenomic evidence of some current antidiabetic agents applied in clinical settings, and highlights potential drugs with new targets for diabetes, which represent a more effective treatment in the future.
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Affiliation(s)
- Zhiwei Zeng
- Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, 361021, China
| | - Shi-Ying Huang
- College of Food and Biological Engineering, Jimei University, Xiamen, 361021, China
| | - Tao Sun
- Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, 361021, China.
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Maekawa Y, Furuie H, Kato M, Myobatake Y, Kamiyama E, Watanabe A, Shiosakai K, Taguchi T, Bass R, Zhou J, Dishy V, Warren V, Vashi V, Ishizuka H. Effect of DS-8500a, a Novel G Protein-Coupled Receptor 119 Agonist, on the Pharmacokinetics of Rosuvastatin and Atorvastatin in Healthy Subjects. Clin Drug Investig 2019; 39:967-978. [DOI: 10.1007/s40261-019-00825-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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