The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing

Recent deorphanization efforts have paired the G-protein-coupled receptors GPR40, GPR41 and GPR43 with fatty acids as endogenous ligands. While carboxylic acids have been historically known to serve as fuel sources and biomarkers of disease, these studies demonstrate that fatty acids can act as sign...

Full description

Saved in:

Bibliographic Details
Published in:	Biochemical Society transactions Vol. 34; no. Pt 5; p. 770
Main Authors:	Covington, D K, Briscoe, C A, Brown, A J, Jayawickreme, C K
Format:	Journal Article
Language:	English
Published:	England 01-11-2006
Subjects:	Animals Diabetes Mellitus - physiopathology Humans Leptin - physiology Metabolic Syndrome - physiopathology Obesity - physiopathology Receptors, Cell Surface - physiology Receptors, G-Protein-Coupled - physiology
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Recent deorphanization efforts have paired the G-protein-coupled receptors GPR40, GPR41 and GPR43 with fatty acids as endogenous ligands. While carboxylic acids have been historically known to serve as fuel sources and biomarkers of disease, these studies demonstrate that fatty acids can act as signalling molecules at the cell-surface level. This receptor subfamily shares approx. 30% identity among members, with some limited cross-over between ligand activities. Generalized expression patterns within the pancreatic beta-cell, adipose depots and the gastrointestinal tract infer involvement in energy source recognition, absorption, storage and/or metabolism. GPR40, activated by medium and long-chain fatty acids, has been shown to potentiate insulin secretion at the beta-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on beta-cell function. GPR41 and GPR43 have been reported to stimulate leptin release and adipogenesis respectively via activation by short-chain fatty acids. These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome.
ISSN:	0300-5127
DOI:	10.1042/bst0340770