Expert opinion on investigational drugs
-
Expert Opin Investig Drugs · Mar 2012
ReviewThe therapeutic potential of GPR119 agonists for type 2 diabetes.
Patients 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. ⋯ GPR119 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.