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曹师承1，赵刚1，常波2，张合1（1中国医科大学基础医学院运动医学基础教研室，辽宁沈阳110001；2沈阳体育学院运动人体科学系，辽宁沈阳110102）摘要：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 ，30mg/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48h ，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。关键词：运动；2型糖尿病；磷脂酰肌醇3激酶；蛋白激酶B中图分类号：R589文献标识码：A 文章编号：1673-4254(2010)06-1217-05Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2diabetic ratsCAO Shi-cheng 1,ZHAO Gang 1,CHANG Bo 2,ZHANG He 11Department of Sports Medicine,College of Basic Medical Sciences,China Medical University,Shenyang 110001,China ;2Department of Human Sports Science,Shenyang Sport University,Shenyang 110102,ChinaAbstract:Objective To investigate the effect of exercise on the expressions of phosphatidylinositol 3kinase (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 2diabetic 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 8weeks of the high-fat diet,each rat received an intraperitoneal injection of streptozotocin (STZ,30mg/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 4weeks;all the groups maintained their assigned diets.The gastrocnemius of all the rats were dissected 48h 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 GLUT4mRNA 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 (P <0.05)and elevated GLUT4protein and mRNA expressions in the skeletal muscles (P <0.01,P <0.05).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 2diabetic rats.Key words:exercise;type 2diabetes;phosphatidylinositol 3kinase;protein kinase B运动提高骨骼肌对胰岛素的敏感性，增加正常机体与2型糖尿病患者吸收和利用葡萄糖，调节血糖平衡［1］。运动疗法已广泛用于2型糖尿病的预防和临床治疗。研究证实，运动通过改善正常机体胰岛素信号通路磷脂酰肌醇3激酶PI3K ）/蛋白激酶B （PKB ）的磷酸化水平与蛋白表达［2-3］，促进骨骼肌细胞葡萄糖转运蛋白4（GLUT4)释放、易位与肌细胞膜融合，增加葡萄糖的吸收与利用，调节糖代谢［4］。然而，2型糖尿病患者不同程度损害骨骼肌胰岛素信号通路级联蛋白激酶的磷酸化［5］，运动是否改善2型糖尿病骨骼肌胰岛素信号通路磷酸化水平，促进葡萄糖吸收的分子机制目前仍未清楚。本研究首先通过高脂饲料喂养大鼠，采用小剂量链脲佐菌素（STZ ）诱导高脂饲料喂养大鼠发展为2型糖尿病［6］，观察运动干预对糖尿病收稿日期：2010-01-12基金项目：国家自然科学基金（30971414）作者简介：曹师承（1958-），男，博士，副教授，E-mail:caoshicheng @tom.com 2010;30(6)南方医科大学学报(J South Med Univ)1217··

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