title: The therapeutic potential of GPR119 agonists for type 2 diabetes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Drug Discovery Research , Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. takahide.ohishi@astellas.com
authors.forename: Takahide
authors.initials: T
authors.lastname: Ohishi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C519854:GPR119 protein, human; D007004:Hypoglycemic Agents; D043562:Receptors, G-Protein-Coupled