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GPR119 as a fat sensor

Harald S Hansen1, Mette M Rosenkilde, Jens J Holst

  • 1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. hsh@farma.ku.dk

Trends in Pharmacological Sciences
|May 8, 2012
PubMed

Insights

The G protein-coupled receptor 119 (GPR119) is a key target for diabetes drug development. Its activation by dietary fats, particularly 2-monoacylglycerol, stimulates insulin and GLP-1 release.

Area of Science:

  • Biochemistry
  • Endocrinology
  • Pharmacology

Background:

  • G protein-coupled receptor 119 (GPR119) is primarily found in pancreatic beta cells and enteroendocrine cells.
  • GPR119 is a significant target for novel anti-diabetic medications, aiming to enhance insulin and GLP-1 secretion.
  • Endogenous lipids, including oleoylethanolamide and oleic acid derivatives, activate GPR119.

Purpose of the Study:

  • To investigate the role of GPR119 in mediating the effects of dietary fats on GLP-1 release.
  • To identify endogenous ligands that activate GPR119 and elucidate their mechanisms of action.
  • To understand the physiological significance of GPR119 activation for glucose homeostasis.

Main Methods:

  • Analysis of GPR119 expression in pancreatic and intestinal tissues.
  • Investigation of GPR119 activation by various endogenous lipids, including 2-monoacylglycerol.
  • Assessment of insulin and GLP-1 release in response to GPR119 agonists.

Main Results:

  • Dietary fat stimulation of GLP-1 release is significantly mediated by the luminal formation of 2-monoacylglycerol acting on GPR119.
  • GPR119 activation in pancreatic beta cells and enteroendocrine cells promotes insulin and GLP-1 secretion, respectively.
  • Endogenous lipids like N-oleoyl-dopamine and 1-oleoyl-lysophosphatidylcholine also activate GPR119.

Conclusions:

  • GPR119 acts as a 'fat sensor' in the gut, linking dietary fat intake to incretin hormone release.
  • Understanding GPR119's endogenous ligands and activation pathways is vital for developing next-generation anti-diabetic drugs.
  • Targeting GPR119 offers a promising therapeutic strategy for managing type 2 diabetes.

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