An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion
| Autor: | Raghavendra G. Mirmira, Medha Priyadarshini, Charles R. Mackay, Thierry Alquier, Annette Gilchrist, Helena Mancebo, Barton Wicksteed, Vincent Poitout, Miles Fuller, Stephanie R. Villa, Brian T. Layden |
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| Rok vydání: | 2015 |
| Předmět: |
endocrine system
medicine.medical_specialty biology Insulin medicine.medical_treatment General Medicine Glucose clamp technique medicine.disease Insulin receptor Endocrinology Insulin resistance Internal medicine Insulin receptor substrate Free fatty acid receptor 2 biology.protein medicine Glucose homeostasis Receptor Molecular Biology |
| Zdroj: | Molecular Endocrinology. 29:1055-1066 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | G protein-coupled receptors have been well described to contribute to the regulation of glucose-stimulated insulin secretion (GSIS). The short-chain fatty acid-sensing G protein-coupled receptor, free fatty acid receptor 2 (FFAR2), is expressed in pancreatic β-cells, and in rodents, its expression is altered during insulin resistance. Thus, we explored the role of FFAR2 in regulating GSIS. First, assessing the phenotype of wild-type and Ffar2−/− mice in vivo, we observed no differences with regard to glucose homeostasis on normal or high-fat diet, with a marginally significant defect in insulin secretion in Ffar2−/− mice during hyperglycemic clamps. In ex vivo insulin secretion studies, we observed diminished GSIS from Ffar2−/− islets relative to wild-type islets under high-glucose conditions. Further, in the presence of acetate, the primary endogenous ligand for FFAR2, we observed FFAR2-dependent potentiation of GSIS, whereas FFAR2-specific agonists resulted in either potentiation or inhibition of GSIS, ... |
| Databáze: | OpenAIRE |
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