| First Author | McNelis JC | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 9 | Pages | 3203-17 |
| PubMed ID | 26023106 | Mgi Jnum | J:246939 |
| Mgi Id | MGI:5923093 | Doi | 10.2337/db14-1938 |
| Citation | McNelis JC, et al. (2015) GPR43 Potentiates beta-Cell Function in Obesity. Diabetes 64(9):3203-17 |
| abstractText | The intestinal microbiome can regulate host energy homeostasis and the development of metabolic disease. Here we identify GPR43, a receptor for bacterially produced short-chain fatty acids (SCFAs), as a modulator of microbiota-host interaction. beta-Cell expression of GPR43 and serum levels of acetate, an endogenous SCFA, are increased with a high-fat diet (HFD). HFD-fed GPR43 knockout (KO) mice develop glucose intolerance due to a defect in insulin secretion. In vitro treatment of isolated murine islets, human islets, and Min6 cells with (S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butanamide (PA), a specific agonist of GPR43, increased intracellular inositol triphosphate and Ca(2+) levels, and potentiated insulin secretion in a GPR43-, Galphaq-, and phospholipase C-dependent manner. In addition, KO mice fed an HFD displayed reduced beta-cell mass and expression of differentiation genes, and the treatment of Min6 cells with PA increased beta-cell proliferation and gene expression. Together these findings identify GPR43 as a potential target for therapeutic intervention. |
