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Modulating GPR40: therapeutic promise and potential in diabetes
Vincent Poitout1, Daniel C-H Lin
1Montreal Diabetes Research Center, CRCHUM, and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
Abstract:
The class A G-protein-coupled receptor GPR40 is predominantly expressed in pancreatic beta cells and plays a major part in fatty acid amplification of glucose-induced insulin secretion. GPR40 agonists are being developed for the treatment of type 2 diabetes. Preclinical studies have shown that GPR40 activation improves glucose control, and recent Phase II trials provided proof-of-concept for this approach. The pharmacology of GPR40 is only partially understood but recent findings suggest that full agonism of the receptor could, in addition to stimulating insulin release, engage the enteroinsular axis. Much remains to be discovered regarding the biology of the receptor to inform the development of GPR40-based drugs.
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