运动对2型糖尿病大鼠骨骼肌胰岛素信号通路PI3K/PKB磷酸化与表达的影响

Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2 diabetic rats

目的探讨运动对2型糖尿病大鼠骨骼肌磷脂酰肌醇3激酶(PI3K)与蛋白激酶B(PKB)磷酸化和蛋白表达及葡萄糖转运蛋白4(GLUT4)和mRNA表达的影响。方法 30只SD雄性大鼠随机分为对照组、糖尿病组与糖尿病运动组。糖尿病组与糖尿病运动组大鼠经高脂饲料喂养8周后,一次性腹腔注射链脲佐菌素(STZ,30 mg/kg),注射后3周确认2型糖尿病建模成功,糖尿病运动组大鼠进行4周游泳训练。糖尿病组与糖尿病运动组大鼠建模过程始终喂养高脂饲料;对照组大鼠喂养普通饲料。糖尿病运动组大鼠4周游泳训练结束,于最后一次运动后恢复48 h,取材各组大鼠腓肠肌。采用Western blot法分析PI3K与PKB的磷酸化水平和蛋白表达,检测GLUT4蛋白表达;RT-PCR检测GLUT4mRNA表达。结果与糖尿病组比较,运动改善2型糖尿病大鼠腓肠肌PKB磷酸化水平与蛋白表达(P<0.05);增加了糖尿病大鼠腓肠肌GLUT4蛋白与mRNA表达(P<0.01,P<0.05)。结论运动可能通过改善2型糖尿病大鼠骨骼肌胰岛素信号通路蛋白激酶磷酸化和蛋白表达,增加对葡萄糖的吸收与利用。

Objective To investigate the effect of exercise on the expressions of phosphatidylinositol 3 kinase（PI3K） and protein kinase B（PKB） phosphorylation,protein and glucose transport proteins（GLUT4） at both the protein and mRNA levels in the skeletal muscles of type 2 diabetic rats.Methods Thirty male SD rats were randomly divided into control group with normal diet feeding,diabetic group and diabetic exercise group with high-fat diet feeding.After 8 weeks of the high-fat diet,each rat received an intraperitoneal injection of streptozotocin（STZ,30 mg/kg）.Three weeks after the injection,the rats were rated for the presence of diabetes,and the rats in the exercise groups took swimming training for 4 weeks;all the groups maintained their assigned diets.The gastrocnemius of all the rats were dissected 48 h after the last training session.Western blotting was applied to detect the phosphorylation and protein expression of PI3K and PKB and the protein expression of GLUT4.The expression of GLUT4 mRNA was determined by RT-PCR.Results Compared with the diabetic group,the diabetic rats in the exercise group showed significantly increased protein expression and phosphorylation of PKB（P0.05） and elevated GLUT4 protein and mRNA expressions in the skeletal muscles（P0.01,P0.05）.Conclusion Exercise training can modulates insulin signal transduction through the protein expression and phosphorylation of the protein kinase to promote glucose uptake in the skeletal muscle of type 2 diabetic rats.