Exenatide抑制2型糖尿病胰岛素抵抗模型大鼠JAK1/STAT1的表达及胰岛B细胞凋亡

目的研究生物活性肽Exenatide对2型糖尿病胰岛素抵抗模型大鼠组织JAK1/STAT1的表达及胰岛B细胞凋亡的影响。方法用低剂量链脲佐菌素(STZ)联合高脂喂养的方法建立胰岛素抵抗大鼠模型,分别用Exenatide、二甲双胍和生理盐水作用于模型大鼠。检测大鼠糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、空腹血糖(FBG)等生化指标、计算胰岛素敏感指数(ISI),观察Exenatide对胰岛素抵抗模型大鼠的疗效。蛋白质印迹法检测大鼠胰岛组织JAK1转录激活子1(STAT1)的蛋白表达水平；Annexin-Ⅴ/PI 染色法比较各组胰岛B细胞对氧化应激诱发的细胞凋亡率。结果与生理盐水对照组相比,Exenatide治疗组ISI增高,糖化血红蛋白降低(P均<0.05)。与生理盐水对照组和二甲双胍治疗组相比,Exenatide组胰岛组织中JAK1/STAT1蛋白表达水平降低 (P<0.01),且H2O2诱发的胰岛B细胞凋亡率降低(P<0.01)。结论Exenatide可能通过调节JAK1/STAT1的表达,改善胰岛素抵抗,抑制B细胞凋亡。

Exenatide inhibits JAK1/STAT1 expression and B cell apoptosis in insulin resistant rat model of type 2 diabetes mellitus

Abstract]ObjectiveTo study the effects of Exenatide on JAK1/STAT1 expression in the islet tissues and apoptosis of pancreatic B-cell in type 2 diabetic rat model with insulin resistance. MethodsInsulin resistant type 2 diabetic rat model was induced by combined treatment with high-fat diet and low-dose streptozotocin. The model rats were treated with Exenatide (Ex), metformin (Met) or normal saline (NS); the serum glycosylated hemoglobin (HbA1c), fasting insulin (FINS),and fasting plasma glucose (FBG) were observed and the insulin sensitivity index was calculated to evaluate the therapeutic effects of Exenatide on insulin resistance. Western blotting analysis was performed to detect the protein expression of JAK1/STAT1 in the islet tissues. Annexin/PI staining assay was used to evaluate B-cell apoptosis induced by oxidative stress. MethodsEx group showed a significantly elevated ISI and a reduced HbA1c level compared with NS group (P<0.05). JAK1/STAT1 expression and H2O2-induced B-cell apoptosis rate were significantly lower in Ex group than in Met and NS groups (P <0.01). MethodsExenatide can improve insulin sensitivity and inhibit B-cell apoptosis, probably by regulating the expression of JAK1/STAT1.