GLP-1对大鼠胰岛细胞增殖及凋亡的影响

Effect of glucagon-like peptide 1 on the proliferation and apoptosis of rat pancreatic islet

目的观察胰升糖素样肽1(GLP-1)对大鼠胰岛细胞增殖及凋亡的影响,并探讨其作用机制。方法(1)GLP-1与大鼠胰岛细胞瘤细胞株RINm5f共育,观察其增殖情况;(2)检测GLP-1对IL-1β诱导的RINm5f细胞凋亡的保护作用;(3)GLP-1与原代培养大鼠胰岛细胞共育1、3、5天后,检测BAX及Bcl-2基因的表达。结果(1)随着GLP-1浓度增高及刺激时间延长,RINm5f细胞A值呈剂量及时间依赖性增加;(2)GLP-1组与对照组相比RINm5f细胞凋亡率显著下降(P<0.05);(3)与GLP-1共育后,大鼠胰岛BAX基因的表达量无明显变化,对照组BAX基因的表达逐渐增加(P<0.05);而Bcl-2基因的表达量随着与GLP-1共育时间的延长呈时间依赖性增加。结论GLP-1对大鼠胰岛细胞增殖有明显促进作用;同时对胰岛细胞的凋亡有保护作用。

Objective To investigate the effect of glucagon-like peptide I（GLP-1） on the proliferation and apoptosis of rat pancreatic islets. Methods （1） The cell line of rat insulinoma （RINm5f） was cultured with different concentrations of GLP-1 for certain durations or co-cultured with GLP-1 for various periods. Cell proliferation was assessed by MTT colorimetric assay. （2） IL-1β was used to induce the apoptosis of RINm5f, and the anti-apoptosis effect of GLP-1 was detected by flow cytometry. （3） The isolated rat islets were co-cultured with 10 nmol/L GLP-1 for 1, 3, 5 days, respectively. Total RNA was extracted and the expressions of BAX and Bcl-2 genes were detected by RT-PCR. Results （1） GLP-1 increased the proliferation of the cell line in a dose-and time-dependent fashion. （2） IL-1β could induce the apoptosis of RINm5f and GLP-1 showed significant protective effect on cytokine-induced cell apoptosis. （3） Compared with the control group, Bcl-2 gene expression increased in a time-dependent manner when co-cultured with GLP-1 and reached the peak level on the 5th day. On the contrary, the BAX gene expression was not markedly changed when co-cultured with GLP-1. Conclusions GLP-1 could promote the proliferation of pancreatic islets. Meanwhile, it could reduce the apoptosis of pancreatic islets by means of regulating Bcl-2 and BAX gene expressions.