|Stimulating beta-Cell Replication and Improving Islet Graft Function by AR231453, A GPR119 Agonist|
|Gao, J.5,6,7; Tian, L.4,6,7; Weng, G.3,6,7; O′ Brien, T. D.2; Luo, J.1; Guo, Z.6,7|
|收录类别||SCI ; ISTP|
|WOS标题词||Science & Technology|
|类目[WOS]||Immunology ; Surgery ; Transplantation|
|研究领域[WOS]||Immunology ; Surgery ; Transplantation|
|关键词[WOS]||GLYCEMIC CONTROL ; MICE ; TRANSPLANTATION ; PROLIFERATION ; RELEASE ; AGE|
Objective. G protein-coupled receptor 119 (GPR119) is predominantly expressed in beta cells and intestinal L cells. AR231453 is a selective small-molecular GPR119 agonist that enhances glucose-dependent insulin secretion and glucagon-like peptide 1 (GLP-1) release. We investigated whether AR231453 can directly stimulate beta-cell replication and improve islet graft function in diabetic mice.
Methods. A total of 100 syngenic C57BL16 mouse islets were transplanted under the left kidney of each chemically induced diabetic C57BL16 mouse. Starting from the day of transplantation, these recipients were given bromodeoxyuridine (BrdU) daily with or without AR231453 at 10 mg/kg/d. Islet graft function was monitored by measuring blood glucose levels. At 4 weeks, left nephrectomy was performed to remove the kidney bearing the islet grafts to determine beta-cell replication in the islet grafts. Insulin and BrdU immunofluorescence staining was performed to detect replicated beta cells. Insulin(+) and BrdU(+) beta cells in islet grafts were counted using a confocal microscope. To determine whether AR231453 increases plasma GLP-1 levels, we collected plasma from AR231453 treated mice at 30 minutes after treatment and measured plasma active GLP-1 by enzyme-linked immunosorbent assay.
Results. Although all recipient mice achieved normoglycemia at 28 days with or without treatment, normoglycemia was achieved in significantly fewer days in AR231453-treated mice. The vehicle-treated mice achieved normoglycemia in 16 +/- 6 days, while AR231453-treated mice only required only 8 +/- 3 days (P <.01). The percentage of insulin(+) and BrdU(+) beta cells in islet grafts was significantly higher in AR231453-treated mice than in vehicle-treated mice. The mean percentage of insulin(+) and BrdU(+) beta cells in islet grafts was 21.5% +/- 6.9% in AR231453-treated mice and 5.6% +/- 3.7% in vehicle-treated mice (P <.01). The plasma active GLP-1 levels were also significantly higher in AR231453-treated mice than in vehicle-treated mice (P <.05).
Conclusion. Our data demonstrate that AR231453, a GPR119 agonist, can stimulate beta-cell replication and improve islet graft function.
|作者单位||1.NGM Biopharmaceut Inc, San Francisco, CA USA|
2.Univ Minnesota, Dept Vet Populat Med, Minneapolis, MN USA
3.Ningbo Univ, Yinzhou Hosp 2, Dept Urol, Ningbo 315211, Zhejiang, Peoples R China
4.Guangxi Med Univ, Affiliated Hosp 1, Dept Surg, Nanning, Peoples R China
5.Peking Univ, Peoples Hosp, Dept Hepatobiliary Surg, Beijing 100871, Peoples R China
6.Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
7.Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA
|Gao, J.,Tian, L.,Weng, G.,et al. Stimulating beta-Cell Replication and Improving Islet Graft Function by AR231453, A GPR119 Agonist[J]. TRANSPLANTATION PROCEEDINGS,2011,43(9):3217-3220.|
|APA||Gao, J..,Tian, L..,Weng, G..,O&prime.,Brien, T. D..,...&Guo, Z..(2011).Stimulating beta-Cell Replication and Improving Islet Graft Function by AR231453, A GPR119 Agonist.TRANSPLANTATION PROCEEDINGS,43(9),3217-3220.|
|MLA||Gao, J.,et al."Stimulating beta-Cell Replication and Improving Islet Graft Function by AR231453, A GPR119 Agonist".TRANSPLANTATION PROCEEDINGS 43.9(2011):3217-3220.|