Stimulating beta cell replication and improving islet graft function by GPR119 agonists

Transpl Int. 2011 Nov;24(11):1124-34. doi: 10.1111/j.1432-2277.2011.01332.x. Epub 2011 Sep 8.


G protein-coupled receptor 119 (GPR119) is predominantly expressed in β cells and intestinal L cells. In this study, we investigated whether oleoylethanolamide (OEA), a GPR119 endogenous ligand, and PSN632408, a GPR119 synthetic agonist, can stimulate β-cell replication in vitro and in vivo and improve islet graft function in diabetic mice. We found that OEA and PSN632408 significantly increased numbers of insulin(+)/5-bromo-2'-deoxyuridine (BrdU)(+) β cells in cultured mouse islets in a dose-dependent manner. All diabetic recipient mice, given marginal syngeneic islet transplants with OEA or PSN632408 or vehicle, achieved normoglycemia at 4 weeks after transplantation. However, normoglycemia was achieved significantly faster in OEA- or PSN632408-treated diabetic mice than in vehicle-treated diabetic mice (P < 0.05). The percentage of insulin(+)/BrdU(+) β cells in islet grafts in OEA- and PSN632408-treated mice was significantly higher than in vehicle-treated mice (P < 0.01). Our data demonstrated that OEA and PSN632408 can stimulate β-cell replication in vitro and in vivo and improve islet graft function. Targeting GPR119 is a novel therapeutic approach to increase β-cell mass and to improve islet graft function by stimulating β-cell replication.

MeSH terms

  • Acids, Heterocyclic / pharmacology
  • Animals
  • Cell Division / drug effects
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / surgery*
  • Endocannabinoids
  • Glucagon-Like Peptide 1 / blood
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans Transplantation / methods*
  • Mice
  • Mice, Inbred C57BL
  • Oleic Acids / pharmacology
  • Oxadiazoles / pharmacology
  • Receptors, G-Protein-Coupled / agonists*


  • Acids, Heterocyclic
  • Endocannabinoids
  • Gpr119 protein, mouse
  • Oleic Acids
  • Oxadiazoles
  • PSN 632408
  • Receptors, G-Protein-Coupled
  • oleoylethanolamide
  • Glucagon-Like Peptide 1