Modulating GPR40: therapeutic promise and potential in diabetes

Drug Discov Today. 2013 Dec;18(23-24):1301-8. doi: 10.1016/j.drudis.2013.09.003. Epub 2013 Sep 16.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Design
  • Fatty Acids / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism


  • Blood Glucose
  • FFAR1 protein, human
  • Fatty Acids
  • Hypoglycemic Agents
  • Insulin
  • Receptors, G-Protein-Coupled