title: Stimulating beta cell replication and improving islet graft function by GPR119 agonists.
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.
authors: Department of Surgery and Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
authors: Jie
authors: J
authors: Gao
authors: Lei
authors: L
authors: Tian
authors: Guobin
authors: G
authors: Weng
authors: Nicholas V
authors: NV
authors: Bhagroo
authors: Robert L
authors: RL
authors: Sorenson
authors: Timothy D
authors: TD
authors: O'Brien
authors: Jian
authors: J
authors: Luo
authors: Zhiguang
authors: Z
authors: Guo
mesh_terms: D000147:Acids, Heterocyclic / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000601:surgery*; D063388:Endocannabinoids; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*
chemical_list: D000147:Acids, Heterocyclic; D063388:Endocannabinoids; C516207:Gpr119 protein, mouse; D009829:Oleic Acids; D010069:Oxadiazoles; C534146:PSN 632408; D043562:Receptors, G-Protein-Coupled; C488250:oleoylethanolamide; D052216:Glucagon-Like Peptide 1