ArticleDiabetes2009
Deletion of GPR40 impairs glucose-induced insulin secretion in vivo in mice without affecting intracellular fuel metabolism in islets.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 123 citations in OpenAlex.
- Effects of Hypertriglyceridemia With or Without NEFA Elevation on β-cell Function and Insulin Clearance and Sensitivity.The Journal of clinical endocrinology and metabolism · 2025Article
- Modern Approaches to Diabetes: The Role of Phytochemicals in Targeting Molecular Receptors.Current topics in medicinal chemistry · 2025Review
- Evaluating the impact of lipids in isolated islet research.Frontiers in endocrinology · 2025Review
- Metabolic and Molecular Amplification of Insulin Secretion.Advances in anatomy, embryology, and cell biology · 2024Review
- Novel targets for potential therapeutic use in Diabetes mellitus.Diabetology & metabolic syndrome · 2023Review
- β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood.JCI insight · 2022Article
- The role of free fatty acid receptor pathways in a selective regulation of TRPA1 and TRPV1 by resolvins in primary sensory neurons.Journal of cellular physiology · 2022Article
- Plin5, a New Target in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Review
- Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC).Journal of cellular physiology · 2021Article
- Chemogenetic approaches to identify metabolically important GPCR signaling pathways: Therapeutic implications.Journal of neurochemistry · 2021Review
- Olive Oil Lipophenols Induce Insulin Secretion in 832/13 β-Cell Models.Pharmaceutics · 2021Article
- Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes.Annals of the New York Academy of Sciences · 2020Review
- Disrupted Lipid Raft Shuttling of FcεRI by n-3 Polyunsaturated Fatty Acid Is Associated With Ligation of G Protein-Coupled Receptor 120 (GPR120) in Human Mast Cell Line LAD2.Frontiers in nutrition · 2020Article
- GPR40 activation initiates store-operated CaScientific reports · 2019Article
- Selective activation of GMolecular metabolism · 2019Article
- Review
- Article
- Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets.European journal of nutrition · 2018Article
- FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice.Endocrinology · 2018Article
- The MPLEx Protocol for Multi-omic Analyses of Soil Samples.Journal of visualized experiments : JoVE · 2018Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveThe G-protein-coupled receptor GPR40 mediates fatty acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. RESEARCH DESIGN AND
methodsInsulin secretion and sensitivity were assessed in GPR40 knockout mice and their wild-type littermates by hyperglycemic clamps and hyperinsulinemic euglycemic clamps, respectively. Transcriptomic analysis, metabolic studies, and lipid profiling were used to ascertain whether GPR40 modulates intracellular fuel metabolism in islets.
resultsBoth glucose- and arginine-stimulated insulin secretion in vivo were decreased by approximately 60% in GPR40 knockout fasted and fed mice, without changes in insulin sensitivity. Neither gene expression profiles nor intracellular metabolism of glucose and palmitate in isolated islets were affected by GPR40 deletion. Lipid profiling of isolated islets revealed that the increase in triglyceride and decrease in lyso-phosphatidylethanolamine species in response to palmitate in vitro was similar in wild-type and knockout islets. In contrast, the increase in intracellular inositol phosphate levels observed in wild-type islets in response to fatty acids in vitro was absent in knockout islets.
conclusionsThese results indicate that deletion of GPR40 impairs insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism in islets, via a mechanism that may involve the generation of inositol phosphates downstream of GPR40 activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.