title: GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity.
abstract: BACKGROUND
  GPR119 is a Gαs-protein-coupled receptor expressed predominantly in pancreatic islets and gastrointestinal tract in humans.
  
  
  OBJECTIVE
  To review the available literature on GPR119 agonists.
  
  
  RESULTS
  GPR119 de-orphanisation indicates two classes of possible endogenous agonists, phospholipids and fatty acid amides, with oleoylethanolamide and N-oleoyldopamine being the most potent. GPR119 agonists increase intracellular cAMP leading to increased glucose-dependent insulin secretion from pancreatic β-cells and incretin secretion from gut enteroendocrine cells. In various animal models of type 2 diabetes and obesity, orally available, potent, selective, synthetic GPR119 agonists: i) lower blood glucose without hypoglycaemia; ii) slow diabetes progression; and iii) reduce food intake and body weight.
  
  
  CONCLUSIONS
  Oral GPR119 agonists may have the potential to achieve blood glucose control together with body weight loss in type 2 diabetics, an outcome only achievable currently with injectable glucagon-like peptide 1 receptor agonists.
authors.affiliation: Director, Chemistry (OSI) Prosidion, Windrush Court, Watlington Road, Oxford, OX4 6LT, UK.
authors.forename: Matthew Ct
authors.initials: MC
authors.lastname: Fyfe
authors.forename: James G
authors.initials: JG
authors.lastname: McCormack
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Overton
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Procter
authors.forename: Christine
authors.initials: C
authors.lastname: Reynet