胃转流术对2型糖尿病大鼠胰岛细胞胰岛素受体及胰岛素受体底物2表达的影响

Influence of gastric bypass on expressions of insulin receptor and insulin receptor substrate 2 in islet cells of rats with type 2 diabetes mellitus

目的:探讨胃转流术对2型糖尿病大鼠胰岛细胞中胰岛素受体(IRc)及胰岛素受体底物2(IRS-2)表达的影响。方法:高糖高脂饮食联合腹腔注射小剂量链脲佐菌素建立2型糖尿病大鼠模型,将造模成功的大鼠分为模型组和胃转流组,另取正常大鼠作为正常对照组,胃转流组大鼠行胃空肠吻合术加空肠侧侧吻合,模型组与正常对照组大鼠均行假手术。检测术前及术后8周大鼠空腹血糖、血清胰岛素,计算胰岛素敏感指数(ISI),用免疫组化法检测胰腺组织IRc及IRS-2的表达。结果:与正常对照组比较,模型组与胃转流组术前空腹血糖均明显升高,ISI均明显降低,但术后胃转流组两项指标均较模型组明显改善(均P<0.05);各组胰岛素水平手术前后均无统计学差异(均P>0.05)。术后8周,胃转流组胰岛细胞IRc和IRS-2表达量均明显高于模型组(均P<0.05),其中IRc表达量仍低于正常对照组(P<0.05),但IRS-2表达量与正常对照组接近(P>0.05)。结论:2型糖尿病大鼠胰岛细胞中IRc及IRS-2表达下调,而胃转流术能够使其表达显著增加,这可能是该手术产生对2型糖尿病产生疗效的机制之一。

Objective：To investigate the influence of gastric bypass surgery on expressions of insulin receptor（IRc） and insulin receptor substrate 2（IRS-2） in islet cells of rats with type 2 diabetes mellitus.Methods：The model of type 2 diabetes mellitus in rats was induced by a high fat and high glucose diet plus intraperitoneal streptozotocin injection,and then the rats with establishment of successful model were divided into model group and gastric bypass group,using the normal rats as normal control group.The rats in gastric bypass group underwent gastrojejunostomy and side-to-side jejunojejunostomy,and those in model group and normal control group underwent sham operation.The fasting glucose and serum insulin levels were measured and insulin sensitivity index（ISI） was calculated before and at 8 weeks after operation,and the IRc and IRS-2expressions in pancreatic tissues were determined by immunohistochemical staining.Results：The fasting glucose levels were increased and ISI values were decreased significantly in both model group and gastric bypass group compared with normal control group before operation,but these two parameters were significantly improved in gastric bypass group compared with model group after operation（all P〈0. 05）;the serum insulin levels showed no significantly difference among groups before and after operation（both P〈0. 05）.In gastric bypass group at 8 weeks after operation,both IRc and IRS-2 expression levels were significantly higher than those in model group（both P〉0. 05）,but IRc expression level was still lower than that in normal control group（P〈0. 05）,while IRS-2 expression level was approximately equal to that in normal control group（P〉0. 05）.Conclusion：IRc and IRS-2 expressions are decreased in islet cells of rats with type 2 diabetes mellitus,and gastric bypass surgery can increase IRc and IRS-2 expression,which may be one of the mechanisms for the therapeutic effect of this surgical procedure on type 2 diabetes mellitus.