Exendin-4对STZ糖尿病大鼠胰岛细胞IRS-2表达的影响

目的观察Exendin-4对链脲佐菌素（STZ）糖尿病大鼠空腹血糖（FBG）、胰岛素、胰岛β细胞增殖率和胰岛素受体底物2（IRS-2）表达的影响。方法SD大鼠高糖高脂饲料喂养结合腹腔注射小剂量STZ（35mg／kg）制备STZ糖尿病大鼠模型，随机分成糖尿病组及Exendin-4治疗低、中、高剂量组，并设立正常对照组。Ex—endin-4给药6周后处死大鼠，心脏取血测FBG、糖化血红蛋白（HbA1c）、胰岛素，取胰腺组织切片作苏木精-伊红染色和胰岛素、IRS-2、增殖细胞核抗原（PCNA）免疫组化染色，计算稳态模型胰岛素抵抗指数（HOMA—IR）及胰岛β细胞增殖率。结果Exendin-4各治疗组IRS-2及β细胞的增殖率较糖尿病组增加（P〈0．05）；Exendin-4高剂量组与糖尿病组比较，FBG和HbA1c水平明显降低（P〈0．01），HOMA—IR指数改善。结论Exendin-4能够促进糖尿病大鼠胰岛β细胞增殖，改善血糖代谢和胰岛素抵抗，其机制可能与IRS-2表达上调有关。

Effects of exendin-4 on the expression of IRS-2 of pancreatic β cells in STZ diabetic rat islet

Objective To investigate the effects of exendin - 4 on fasting blood glucose （ FBG）, insulin and proliferation rate of pancreatic β cells as well as the expression of insulin receptor substrates 2 （ IRS - 2） of STZ diabetic rats. Methods The model of STZ diabetic rats was established by high fat diet and intraperitoneal injection of low dose STZ （35 mg/kg）. The diabetic rats were randomized into 4 groups： diabetes mellitus （DM） group, low dose of exendin -4 （EL） group, middle dose of exendin - 4 （EM） group and high dose of exendin - 4 （EH） group. Normal control （NC） group was also simultaneously established. 6 weeks after exendin -4 administration, the rats in the five groups were sacrificed, and the levels of FBG, HbAlc and insulin from the cardiac blood were determined. In addition to HE method, pancreatic tissue sections of rats were stained by immunostaining with the marker of insulin, PCNA and IRS - 2 for the calculation of HOMA - IR and proliferation rate of pancreatic β cells. Results Compared with DM group, IRS - 2 and the proliferation rate of pancreatic β cells of the Exendin - 4 groups （ EL, EM and EH） increased （ P 〈 0.05 ） ; compared with DM group, FBG, HbA1 c and HOMA - IR in EH group evidently decreased （ P 〈 0.01 or P 〈 0.05 ）. Conclusion Exendin -4 can promote pancreatic β cell proliferation and improve glucose metabolism and insulin resistance, which might be involved in the up - regulation of IRS - 2 expression.