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GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity Overton HA; Fyfe MC; Reynet CBr J Pharmacol 2008[Mar]; 153 Suppl 1 (Suppl 1): S76-81GPR119 is a G protein-coupled receptor expressed predominantly in the pancreas (beta-cells) and gastrointestinal tract (enteroendocrine cells) in humans. De-orphanization of GPR119 has revealed two classes of possible endogenous ligands, viz., phospholipids and fatty acid amides. Of these, oleoylethanolamide (OEA) is one of the most active ligands tested so far. This fatty acid ethanolamide is of particular interest because of its known effects of reducing food intake and body weight gain when administered to rodents. Agonists at the GPR119 receptor cause an increase in intracellular cAMP levels via G(alphas) coupling to adenylate cyclase. In vitro studies have indicated a role for GPR119 in the modulation of insulin release by pancreatic beta-cells and of GLP-1 secretion by gut enteroendocrine cells. The effects of GPR119 agonists in animal models of diabetes and obesity are reviewed, and the potential value of such compounds in future therapies for these conditions is discussed.|Animals[MESH]|Anti-Obesity Agents/*pharmacology/*therapeutic use[MESH]|Diabetes Mellitus, Type 2/*drug therapy/genetics[MESH]|Glucose/metabolism[MESH]|Homeostasis/drug effects/physiology[MESH]|Humans[MESH]|Hypoglycemic Agents/*pharmacology/*therapeutic use[MESH]|Insulin Resistance[MESH]|Obesity/*drug therapy/genetics[MESH]|Receptors, G-Protein-Coupled/agonists/antagonists & inhibitors/*drug effects/genetics[MESH] |
