metabolic disorders
Metabolic disorders
GPR119 agonists in Diabetes

Pharmacological treatments of Type 2 diabetes involves use of drugs that either improve insulin sensitivity or increase insulin secretion from pancreatic beta cells. Agents that enhance insulin secretion in a glucose-dependent manner or through an elevation of glucagon-like peptide-1 (GLP-1) are desirable as they are not associated with the risk of causing hypoglycemia unlike insulin-mimetics. As part of the efforts dedicated towards controlling Type-2 diabetes, the G-protein-coupled receptor (GPR119) has received considerable attention because of evidence from pre-clinical studies that its modulation may influence parameters related to diabetes. Intervention through G protein-coupled receptor 119 (GPR119) represents a novel strategy for achieving optimal glycemic control.

GPR119 is predominantly expressed in the intestine and pancreatic islets thereby limiting the toxicities commonly encountered with other anti-diabetic or anti-obesity agents. Although the exact mechanism of action is not fully elucidated, it appears that stimulation of GLP-1 intestinal L-cells compounded with an increase in insulin secretion from pancreatic beta cells directly via cAMP is responsible for the beneficial effects observed in animal models. GPR119 agonists therefore represent a new class of therapeutics for Type 2 diabetes and associated disorders with potential to exert a beneficial effect beyond improvement of glucose homeostasis alone.

Overton, H. A. et al. (2008) Br. J. Pharmacology. 153: S76-S81.
Yoshida, S. et al. (2011) Diabetes, Obesity and Metabolism. 13: 34-41.
Current Status : Pre-Clinical