Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2
G Tolhurst, H Heffron, YS Lam, HE Parker, AM Habib… - Diabetes, 2012 - Am Diabetes Assoc
G Tolhurst, H Heffron, YS Lam, HE Parker, AM Habib, E Diakogiannaki, J Cameron…
Diabetes, 2012•Am Diabetes AssocInterest 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 …
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 …
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.
Am Diabetes Assoc