1. Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2
- Author
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Fiona M. Gribble, Abdella M. Habib, Frank Reimann, Eleftheria Diakogiannaki, Helen E. Parker, Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Johannes Grosse, Jennifer Cameron, Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
- Subjects
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 - Abstract
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.
- Published
- 2012