中文摘要：

目的：探讨高浓度葡萄糖对胰岛β细胞胰岛素信号通路信号中胰岛素受体底物2（insulinreoeptorsubstance2，Irs2）、叉头框转录因子1（forkheadtranscriptionfactors01，Fox01）表达的影响。方法：胰岛β细胞株NIT-1细胞培养48h后，随机分为不同葡萄糖浓度（5．6，11．1，16．7，22．5，27．6mmol／L）组，继续培养3d后终止，用MTT比色法检测细胞增殖，免疫荧光法检测细胞凋亡，放射免疫分析方法检测胰岛素水平，Real—TimePCR法检测Irs2、Fox01mRNA变化。结果：（1）在葡萄糖浓度为11．1mmol／L时，NIT-1细胞增殖活性最强、细胞凋亡率最低，胰岛素分泌水平最高。随着葡萄糖浓度升高，细胞增殖活性和胰岛素分泌水平明显下降，细胞凋亡率逐渐增高。当葡萄糖浓度达27．6mmol／L时，细胞增殖活性和胰岛素分泌水平达最低，细胞凋亡率达到最高。（2）葡萄糖浓度为11．1mmol／L时，Irs2mRNA的转录达到最高水平，随着葡萄糖浓度的增高，Irs2mRNA的转录水平呈现逐渐减少趋势；FoxO1基因的mRNA转录水平则随着葡萄糖浓度的增高呈不断增加状态。结论：在高浓度葡萄糖条件下，葡萄糖“毒性”作用通过下调Irs2mRNA表达、增加核内的FoxO1mRNA表达以调节胰岛G细胞的功能及增殖和凋亡，分子间均有其独立的调控机制，同时又相互关联。

英文摘要：

Objective：To evaluate the effects of high concentration of glucose on insulin receptor substance 2 （Irs2） and forkhead transcription factors O1 （FoxO1） expression of pancreatic β cells. Methods： Pancreatic cell lines NIT-1 cells were cultured 48 hours, then were randomly divided into 1 to 5 groups, were cultured with 10%0 FBS DMEM medium containing glucose of 5.6, 11.1, 16.7, 22.5 and 27.6 mmol/L for 3 days. The expression of Its2 and FoxO1 mRNA in the cells was analyzed using the real-time PCR. Cell proliferation was determined by MTT, cell apoptosis was observed by immunofluorescence staining, and insulin secretion was detected by radioimmunoassay. Results： Cell proliferation and insulin secretory function in mouse NIT-1 cells were the best at the concentration of 11.1 mmol/L glucose, and cell apoptosis was the worst. With the increase of glucose concentration, cell proliferation and insulin secretion reduced obviously, the cell apoptosis increased gradually. Under the 27.6 mrnol/L glucose concentration, the pro-liferation rate and insulin lowest, the apoptosis rate secretion level were the was the best. Under the 11.1 mmol/L glucose concentration, Irs2 mRNA expression level was the best, with the increase of glu- cose concentration, it was decreased, but FoxO1 mRNA expression level was increased. Conclusion. With high concentration of glucose, glucose toxicity can re-duce Irs2 mRNA expression, increase FoxO1 mRNA expression of nuclear, regulate functional and survival of pancreatic β cells. They have independent molecular regulatory mechanism but relate each other.