Open AccessStimulating beta cell replication and improving islet graft function by GPR119 agonists
Author(s) -
Gao Jie,
Tian Lei,
Weng Guobin,
Bhagroo Nicholas V.,
Sorenson Robert L.,
O’Brien Timothy D.,
Luo Jian,
Guo Zhiguang
Publication year - 2011
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2011.01332.x
Subject(s) - islet , in vivo , transplantation , endocrinology , medicine , insulin , in vitro , beta cell , streptozotocin , cell , agonist , diabetes mellitus , receptor , biology , biochemistry , microbiology and biotechnology
Summary 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.