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 β-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 β-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on β-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.
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October 2006
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Conference Article|
October 25 2006
The G-protein-coupled receptor 40 family (GPR40–GPR43) and its role in nutrient sensing
D.K. Covington;
D.K. Covington
1
*Department of Molecular Pharmacology, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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C.A. Briscoe;
C.A. Briscoe
†Diabetes Biology Department, Pfizer, 10578 Science Center Drive, San Diego, CA 92121, U.S.A.
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A.J. Brown;
A.J. Brown
‡Department of Screening and Compound Profiling, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.
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C.K. Jayawickreme
C.K. Jayawickreme
§Department of Screening and Compound Profiling, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, U.S.A.
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Publisher: Portland Press Ltd
Received:
June 21 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (5): 770–773.
Article history
Received:
June 21 2006
Citation
D.K. Covington, C.A. Briscoe, A.J. Brown, C.K. Jayawickreme; The G-protein-coupled receptor 40 family (GPR40–GPR43) and its role in nutrient sensing. Biochem Soc Trans 1 October 2006; 34 (5): 770–773. doi: https://doi.org/10.1042/BST0340770
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