Glucose metabolism-related protein 1 (GMRP1) regulates pancreatic beta cell proliferation and apoptosis via activation of Akt signalling pathway in rats and mice
Glucose metabolism-related protein 1 (GMRP1) regulates pancreatic beta cell proliferation and apoptosis via activation of Akt signalling pathway in rats and mice
复制标题
葡萄糖代谢相关蛋白 1 (GMRP1) 通过激活 Akt 信号通路调节大鼠和小鼠胰腺 β 细胞增殖和凋亡
DOI：
10.1007/s00125-011-2048-1
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发表时间：
2011-04-01
期刊：
影响因子：
8.2
通讯作者：
Hu, R.
中科院分区：
文献类型：
--
作者：
Wang, X.;Liu, Y.;Hu, R.
目的/hypothesisWe试图阐明的影响和可能的机制，葡萄糖代谢相关蛋白1（GMRP 1）影响β细胞survival.MethodsAdenovirus-mediated GMRP 1的过度生产和siRNA介导的敲低进行在INS-1 E细胞和大鼠胰岛，细胞增殖或凋亡后，测定，Akt和BCL 2相关的激动剂的细胞死亡（BAD）的磷酸化的影响。INS-1 E细胞和大鼠胰岛在5.6（低）或25 mmol/l（高）葡萄糖培养24或48 h，细胞增殖或凋亡和GMRP 1水平进行了研究。用0、10、50和100 nmol/l胰岛素处理INS-1 E细胞24 h，测定GMRP 1水平。将siRNA转染INS-1 E细胞72 h后，观察高糖对INS-1 E细胞增殖和胰岛素刺激Akt磷酸化的影响。建立葡萄糖输注大鼠模型，并评估β细胞增殖和质量。在葡萄糖灌注的胰岛中测定GMRP 1水平以及Akt和BAD的磷酸化。GMRP 1介导的Akt通路也调查indb/db mice. ResultsGMRP 1的过度生产促进β细胞增殖通过增加Akt的磷酸化。Gmrp 1（也称为Btbd 10）的敲低降低了Akt的磷酸化，增强了β细胞凋亡。高糖增加INS-1 E细胞和胰岛细胞中GMRP 1水平和细胞增殖。Gmrp 1的敲低降低了高糖诱导的细胞增殖和胰岛素刺激的Akt磷酸化。增加的GMRP 1水平参与了葡萄糖输注胰岛中β细胞增殖和质量的增强。结论：GMRP 1通过激活Akt信号通路调节胰岛β细胞的增殖和凋亡。
Aims/hypothesisWe attempted to elucidate the impacts on and possible mechanisms by which glucose metabolism-related protein 1 (GMRP1) affects beta cell survival.MethodsAdenovirus-mediated GMRP1 overproduction and siRNA-mediated knockdown were performed in INS-1E cells and rat islets, after which cell proliferation or apoptosis were determined, and phosphorylation of Akt and BCL2-associated agonist of cell death (BAD) investigated. INS-1E cells and rat islets were cultured at 5.6 (low) or 25 mmol/l (high) glucose for 24 or 48 h, and cell proliferation or apoptosis and GMRP1 levels were investigated. INS-1E cells were treated for 24 h with 0, 10, 50 and 100 nmol/l insulin, and GMRP1 levels were determined. After INS-1E cells were transfected with siRNA for 72 h, high glucose-induced cell proliferation and insulin-stimulated Akt phosphorylation were investigated. Glucose-infused rat models were established and beta cell proliferation and mass were evaluated. Levels of GMRP1, and phosphorylation of Akt and BAD were determined in glucose-infused islets. The GMRP1-mediated Akt pathway was also investigated indb/dbmice.ResultsOverproduction of GMRP1 promoted beta cell proliferation via increased phosphorylation of Akt. Knockdown ofGmrp1(also known asBtbd10) reduced phosphorylation of Akt with enhanced beta cell apoptosis. High glucose increased GMRP1 levels and cell proliferation in INS-1E cells and islet cells. Knockdown ofGmrp1decreased high glucose-induced cell proliferation and insulin-stimulated Akt phosphorylation. Increased GMRP1 levels were involved in the enhancement of beta cell proliferation and mass in glucose-infused islets. Decreased GMRP1 levels may participate in beta cell apoptosis ofdb/dbmice.Conclusions/interpretationGMRP1 regulates pancreatic beta cell proliferation and apoptosis via activation of Akt signalling pathway.