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

Jie Gao1, Lei Tian, Guobin Weng

  • 1Department of Surgery and Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.

Transplant International : Official Journal of the European Society for Organ Transplantation
|September 10, 2011
PubMed

Insights

Oleoylethanolamide (OEA) and a GPR119 agonist stimulated beta-cell replication in vitro and in vivo. This approach improved islet graft function and accelerated normoglycemia in diabetic mice.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Pharmacology

Background:

  • G protein-coupled receptor 119 (GPR119) is expressed in pancreatic beta cells and intestinal L cells.
  • GPR119 plays a role in regulating glucose homeostasis and insulin secretion.
  • Understanding GPR119's function is crucial for developing novel diabetes therapies.

Purpose of the Study:

  • To investigate the effects of the GPR119 endogenous ligand, oleoylethanolamide (OEA), and a synthetic agonist (PSN632408) on beta-cell replication.
  • To evaluate the impact of GPR119 activation on islet graft function in a diabetic mouse model.

Main Methods:

  • In vitro studies using cultured mouse islets to assess beta-cell proliferation.
  • In vivo studies involving marginal syngeneic islet transplantation in diabetic mice.
  • Administration of OEA or PSN632408 to assess effects on normoglycemia and beta-cell replication in grafts.

Main Results:

  • OEA and PSN632408 significantly increased beta-cell replication (insulin+/5-bromo-2'-deoxyuridine (BrdU)+ cells) in cultured islets.
  • Diabetic mice treated with OEA or PSN632408 achieved normoglycemia faster post-islet transplantation compared to controls.
  • Islet grafts in OEA- or PSN632408-treated mice showed a significantly higher percentage of replicating beta cells.

Conclusions:

  • GPR119 activation by OEA or PSN632408 stimulates beta-cell replication both in vitro and in vivo.
  • Targeting GPR119 represents a promising therapeutic strategy for increasing beta-cell mass.
  • Enhancing beta-cell replication via GPR119 agonists can improve islet graft function and glycemic control.

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