【摘要】 目的:观察罗格列酮对实验性2型糖尿病合并高脂血症大鼠骨骼肌组织胰岛素受体底物-1(IRS-1)表达的调节及大鼠骨骼肌细胞葡萄糖转运蛋白4(GLUT4)表达的影响,进一步探讨其可能的作用机制。方法:采用低剂量链脲佐菌素尾静脉注射联合高脂饲料喂养建立2型糖尿病合并高脂血症大鼠模型。未予上述处理的大鼠作为正常对照组,成模大鼠随机分为糖尿病对照组和罗格列酮干预组。药物干预4周后,称重,检测血清葡萄糖、胰岛素、甘油三酯和胆固醇,应用Western印迹法检测大鼠肌肉组织中IRS-1蛋白的表达和细胞膜GLUT4的表达量。结果:(1)罗格列酮干预组大鼠空腹血糖、胰岛素、甘油三酯水平均低于糖尿病对照组(P<0.05),高于正常对照组(P<0.05);罗格列酮干预组血清胆固醇高于正常对照组(P<0.05),与糖尿病对照组差异无显著(P>0.05)。(2)大鼠肌肉细胞膜GLUT4蛋白表达比较:糖尿病对照组明显少于正常对照组,罗格列酮干预组明显多于糖尿病对照组(P<0.05)。(3)大鼠肌肉组织IRS-1蛋白表达量及其酪氨酸磷酸化程度比较:糖尿病对照组明显少于正常对照组,罗格列酮干预组明显多于糖尿病对照组(P<0.05)。结论:罗格列酮可促进大鼠肌肉细胞膜GLUT4的合成增加,可能是通过上调大鼠肌肉组织IRS-1蛋白的表达量及其酪氨酸磷酸化的程度实现的。更多还原

【Abstract】 AIM: To investigate the effect of rosiglitazone on the expressions of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in skeletal muscles of type 2 diabetic rats with hyperlipemia, and to explore the different pharmacological mechanism. METHODS: The model of type 2 diabetic rats with hyperlipemia was established by injecting low dosage of streptozotocin (STZ) and feeding with high fat diet. Then the diabetic rats were divided into two groups: untreated diabetic group and rosiglitazone-intervened diabetic group. The course of treatment lasted for 4 weeks. The expressions of IRS-1 and the GLUT4 proteins in the cell membrane of isolated rats skeletal muscles were detected by Western blotting. RESULTS: The fasting blood glucose, insulin and triglyceride contents in rosiglitazone-intervened diabetic group were lower than those in untreated diabetic group, but they were still higher than those in control group. The result of Western blotting showed that the expression of GLUT4 protein in rosiglitazone-intervened diabetic group was increased compared with untreated diabetic group, but its level was still lower than that in control group. The protein expression and tyrosine phosphorylation of IRS-1 in rosiglitazone-intervened diabetic group were significantly higher than those in untreated diabetic group and their levels were lower than those in control group. CONCLUSION: The effect of rosiglitazone on GLUT4 protein may link to its ability to induce the protein expression and tyrosine phosphorylation of IRS-1 in skeletal muscles in type 2 diabetic rats.更多还原