Year: 2015
Type: article
Abstract: 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. β-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-, Gαq-, and phospholipase C-dependent manner. In addition, KO mice fed an HFD displayed reduced β-cell mass and expression of differentiation genes, and the treatment of Min6 cells with PA increased β-cell proliferation and gene expression. Together these findings identify GPR43 as a potential target for therapeutic intervention.
Source: Diabetes
DOI: 10.2337/db14-1938
Authors: Joanne C. McNelis, Yun Sok Lee, Rafael Mayoral, Rik van der Kant, Andrew M.F. Johnson, Joshua Wollam, Jerrold M. Olefsky
Institution: University of California San Diego
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1462415530, G1605720030, G2041627414, PKA & PKC Targeting Mechanisms (Program Project), INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM, A Gut Microbiome Metabolite Axis in Obesity-Associated Inflammation and Insulin Resistance, Gene Networks controlling macrophage-adipocyte interactions in insulin, Insulin Receptors and the Glucose Transport System, G9000007997, G9000023011, G9000094786, G9000140433, Diabetes Research Center (DRC)
OpenAlex ID: W2132033020