• Takahide Ohishi and Shigeru Yoshida.
• Drug Discovery Research , Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. takahide.ohishi@astellas.com
• Expert Opin Investig Drugs. 2012 Mar 1; 21 (3): 321-8.

IntroductionPatients with type 2 diabetes mellitus (T2DM) are reaching an explosive number. Pancreatic β cell dysfunction is the characteristic feature of the progression of T2DM and there is an increasing need for agents to improve its function. GPR119 is a G protein-coupled receptor (GPCR) expressed both in pancreatic β cells and enteroendocrine cells and has garnered significant interest as a promising target for the next generation of T2DM drug. In vitro studies indicate that GPR119 agonists increase intracellular cAMP levels leading to enhanced glucose-induced insulin release and enhanced incretin hormone glucagon-like peptide 1 (GLP-1) secretion. In T2DM rodent models, GPR119 agonists are shown to decrease blood glucose level and preserve pancreatic β cell function.Areas CoveredThis review summarizes the function of GPR119 and the progresses made in the discovery of GPR119 agonists reported since 2002 in literatures. The importance of GPR119 agonists in glycemic control is discussed.Expert OpinionGPR119 agonists with glucose-dependent insulin release and increased insulin promoter activity is expected to preserve pancreatic β cell function, thereby providing great clinical benefits for T2DM patients. Both the preclinical and clinical data suggest that GPR119 agonist will be a promising anti-diabetic drug.

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