Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2
Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Helen E Parker, Abdella M Habib, Eleftheria Diakogiannaki, Jennifer Cameron, Johannes Grosse, Frank Reimann, Fiona M Gribble, Gwen Tolhurst, Helen Heffron, Yu Shan Lam, Helen E Parker, Abdella M Habib, Eleftheria Diakogiannaki, Jennifer Cameron, Johannes Grosse, Frank Reimann, Fiona M Gribble
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.
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References
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