开郁清胃方对2型糖尿病模型大鼠胰岛细胞胰岛素受体及胰岛素受体底物-1表达的影响

Effect of Kaiyuqingwei Decoction on Expression of Insulin Receptor and Insulin Receptor Substrate-1 in Islets of Type 2 Diabetic Rats

目的研究中药复方开郁清胃方改善2型糖尿病胰岛细胞功能的作用机理。方法以高脂饲料喂养9周加小剂量链脲佐菌素腹腔注射建立2型糖尿病大鼠模型,造模后的动物随机分成模型组、开郁清胃组和文迪雅组,并设立正常对照组。测定空腹血糖、葡萄糖负荷后2h血糖以及糖化血清蛋白、基础胰岛素等,采用高胰岛素正葡萄糖钳夹技术评价整体的胰岛素抵抗,静脉糖耐量试验评估胰岛细胞功能,应用EnVision方法测定胰岛细胞胰岛素和胰岛素受体(IRc)、胰岛素受体底物-1(IRS-1)的表达。结果模型组大鼠同时具有胰岛素抵抗、胰岛素分泌异常和血糖的增高,开郁清胃方和文迪雅都可明显改善模型大鼠的糖代谢和胰岛素的分泌,提高胰岛细胞IRc和IRS-1的表达。结论开郁清胃方可以确切地改善2型糖尿病模型大鼠的糖代谢,其机理包括两个方面,一是外周胰岛素敏感性的提高;二是胰岛细胞功能的改善。对胰岛细胞的胰岛素信号转导的影响是其改善胰岛细胞功能的重要作用机理。

Objective To investigate the mechanism of Chinese herbal medicine compound （Kaiyuqingwei Decoction） improving islet cells function of type 2 diabetes. Methods The models of type 2 diabetic rats were established by feeding with high-fat-diet and injecling low dosage of streptozotocin （15 mg/kg BW）. Rats were randomly divided into model group, Kaiyuqingwei group, and Rosiglitazone group and normal control was established, at the same time, fasting and post-glucose loading 2 hours blood glucose, serum fructosamine and basal insulin were determined. Euglycemic hyperinsulin clamp technique was adopted to evaluate insulin sensitivity of periphery tissues, and intravenous glucose tolerance test to evaluate islets function. Adopting immunohistochemistry stain [EnVision） and computer image analysis technique to determine the expression of insulin, insulin receptor and insulin receptor substrate-1 in islets. Results There were insulin resistance, dysfunction of islet cells and obvious increase of blood glusose in model rats. All these could be improved by Kaiyuqingwei Decoction and Rosiglitazone. Meanwhile, immunohistochemistry stain of islets demonstrated that Kaiyuqingwei Decoction could increase expression of IRc and IRS- 1. Conclusion Kaiyuqingwei Decoction have a certain positive role in improving glucose metabolism of type 2 diabetic rats. The mechanism include two aspects, one is elevation of insulin sensitivity, another is amelioration of dysfunction of islet cells. One of the important mechanisms of amelioration of dysfunction in islet cells is amelioration of insulin signal transduction in pancreatic islets.