Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
| Autor: | Fiona M. Gribble, Abdella M. Habib, Frank Reimann, Eleftheria Diakogiannaki, Helen E. Parker, Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Johannes Grosse, Jennifer Cameron |
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| Přispěvatelé: | Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], Apollo - University of Cambridge Repository |
| Rok vydání: | 2012 |
| Předmět: |
Colon
Endocrinology Diabetes and Metabolism medicine.medical_treatment 030209 endocrinology & metabolism GTP-Binding Protein alpha Subunits Gi-Go Biology Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Glucagon-Like Peptide 1 Free fatty acid receptor 2 Internal Medicine medicine Animals Secretion Receptor 030304 developmental biology G protein-coupled receptor 0303 health sciences Insulin digestive oral and skin physiology Fatty Acids Volatile Glucagon-like peptide-1 3. Good health Mice Inbred C57BL Cytosol Biochemistry Calcium Signal transduction Signal Transduction |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db11-1019 |
| Popis: | Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1–secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes. |
| Databáze: | OpenAIRE |
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