| Autor: |
Tolhurst, Gwen, Heffron, Helen, Lam, Yu Shan, Parker, Helen E, Habib, Abdella M, Diakogiannaki, Eleftheria, Cameron, Jennifer, Grosse, Johannes, Reimann, Frank, Gribble, Fiona M |
| Předmět: |
|
| 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 |
| Externí odkaz: |
|
