Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell Endocrinol. 2013 Apr 30;369(1-2):119-29. doi: 10.1016/j.mce.2013.01.009. Epub 2013 Feb 9.

Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1.

Author information

  • 1Department of Metabolic Disorders, Amgen Inc., South San Francisco, CA 94080, USA.

Abstract

FFA1 (GPR40) and GPR120 are G-protein-coupled receptors activated by long-chain fatty acids. FFA1 is expressed in pancreatic β-cells, where it regulates glucose-dependent insulin secretion, and GPR120 has been implicated in mediating GLP-1 secretion. We show here that FFA1 co-localizes with GLP-1 in enteroendocrine cells and plays a critical role in glucose management by mediating GLP-1 secretion in vivo. Corn oil induces GLP-1 secretion in wild type mice and in GPR120-/- mice, but not in FFA1-/- mice. α-Linolenic acid, an endogenous ligand of FFA1, induces GLP-1 secretion in GLUTag cells and in primary fetal mouse intestinal cells. Synthetic partial FFA1 agonists do not stimulate GLP-1 secretion in mice, but partial and full agonists combined function cooperatively to enhance receptor activation and GLP-1 secretion both in vitro and in vivo. We conclude that allosterism at FFA1 can contribute to postprandial glucose management by stimulating insulin secretion via an extrapancreatic mechanism of action, and that GPR120 in GLP-1 secretion requires further investigation.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk