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

Jie Gao, Lei Tian, Guobin Weng, Nicholas V. Bhagroo, Robert L. Sorenson, Timothy D. O'Brien, Jian Luo, Zhiguang Guo

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1124-1134
Number of pages11
JournalTransplant International
Volume24
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • GLP-1
  • GPR119
  • islet graft function
  • islet transplantation
  • β-cell regeneration
  • β-cell replication

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