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- Title
Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein--Coupled Receptor FFAR2.
- Authors
Tolhurst, Gwen; Heffron, Helen; Yu Shan Lam; Parker, Helen E.; Habib, Abdella M.; Diakogiannaki, Eleftheria; Cameron, Jennifer; Grosse, Johannes; Reimann, Frank; Gribble, Fiona M.
- 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.
- Subjects
FATTY acids; CARBOXYLIC acids; INSULIN; DIABETES; ENDOCRINE diseases
- Publication
Diabetes, 2012, Vol 61, Issue 2, p364
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db11-1019