有氧运动训练8周2型糖尿病模型大鼠骨骼肌磷脂酰肌醇3-激酶-蛋白激酶B信号转导通路的变化

Changes of phosphoinositide 3-kinase-protein kinase B signaling pathway in skeletal muscle of type 2 diabetes rat models after 8-week aerobic exercise

背景:目前普遍观点是2型糖尿病患者胰岛素信号传导中的信号分子磷脂酰肌醇3-激酶和蛋白激酶B相比于健康人群均出现异常,而运动后胰岛素敏感性的改善也与骨骼肌中胰岛素信号传导系统的蛋白表达和活性增强有关。目的:探究8周有氧运动对中龄2型糖尿病大鼠骨骼肌磷脂酰肌醇3-激酶-蛋白激酶B信号转导通路的影响。方法:10个月龄中年雌性SD大鼠75只,由成都达硕实验动物有限公司提供。实验方案经沈阳体育学院科学研究伦理委员会批准(批准号为2015006)。SD大鼠75只随机分成5组:正常对照组,给普通饲料;糖尿病对照1组、糖尿病运动1组,均于高脂饲料喂养8周后注射链脲佐菌素35mg/kg,制备2型糖尿病模型,继续给予高脂饲料至16周;糖尿病对照2组、糖尿病运动2组,均于高脂饲料喂养16周后注射链脲佐菌素35mg/kg,制备2型糖尿病模型;2个运动组均于第9周开始进行有氧运动,运动8周后测试血脂、血糖、胰岛素和腓肠肌磷脂酰肌醇3-激酶-蛋白激酶B的蛋白表达。结果与结论:①8周和16周的高糖高脂饮食结合小剂量的链脲佐菌素均可引发中龄SD大鼠出现骨骼肌磷脂酰肌醇3-激酶、PK蛋白表达下降,磷脂酰肌醇3-激酶-蛋白激酶B信号传导发生障碍,引起脂和糖代谢紊乱,胰岛素敏感性下降,诱发2型糖尿病;②与相对应的糖尿病对照组比较,糖尿病运动1组和糖尿病运动2组的体质量有上升趋势,脂肪量和脂体比有下降趋势,三酰甘油、总胆固醇、游离脂肪酸和低密度脂蛋白值均显著降低,空腹血糖、空腹胰岛素水平显著下降,磷脂酰肌醇3-激酶和蛋白激酶B活性均显著增高;③结果说明,在诱发糖尿病前后施加运动干预,能通过增加机体能量消耗,提高骨骼肌胰岛素信号传导通路磷脂酰肌醇3-激酶-蛋白激酶B磷酸化水平,增加机体胰岛素敏感性,改善脂代谢和糖代谢紊乱,最终对2型糖尿病的发生和发展起到了有效的改善/预防作用。

BACKGROUND:Abnormal phosphoinositide 3-kinase and protein kinase B occurs in insulin signaling transduction of type 2 diabetes,and improvement in insulin sensitivity post-exercise has been shown to be related to the increased protein expression and activity in insulin signaling transduction.OBJECTIVE:To investigate the effect of 8-week aerobic exercise on the phosphoinositide 3-kinase-protein kinase B signaling pathway in type 2 diabetic skeletal muscle of middle-aged rat models.METHODS:Seventy-five 10 month-old female Sprague-Dawley rats were provided by Chengdu Dashuo Experimental Animal Co.,Ltd.,and the study was approved by the Research Ethics Committee of Shenyang Sport University,approval number:2015006.The rats were randomized into five groups:normal control group(common diet),diabetes control 1 group(8-week high fat diet prior to injection of 35 mg/kg streptozotocin;continue to give high fat feed to 16 weeks),diabetes exercise 1 group(8-week high fat diet prior to injection of 35 mg/kg streptozotocin+ aerobic exercise;continue to give high fat feed to 16 weeks),diabetes control 2 group(16-week high fat diet prior to injection of 35 mg/kg streptozotocin),and diabetes exercise 1 group(16-week high fat diet prior to injection of 35 mg/kg streptozotocin+ aerobic exercise).The aerobic exercise was undergone at the 9^th week.The blood lipid,blood glucose,insulin and gastrocnemius phosphoinositide 3-kinase-protein kinase B expression levels were tested after 8 weeks of exercise.RESULTS AND CONCLUSION:(1)Both high-fat and high-fat diets at 8 and 16 weeks combined with low-dose streptozotocin could induce the decrease of phosphoinositide 3-kinase and protein kinase B protein expression in the rat skeletal muscle,and impaired phosphoinositide 3-kinase-protein kinase B signal transduction caused lipid and glucose metabolism disorders,decreased insulin sensitivity,and induced type 2 diabetes.(2)Compared with the diabetes control groups,the body mass in the aerobic exercise groups was on a rise,fat mass and body fat rate were on a descent,triacylglycerol,total cholesterol,free fatty acid and low density lipoprotein were significantly decreased,fasting blood-glucose and fasting insulin levels were significantly decreased,and activities of phosphoinositide 3-kinase and protein kinase B were significantly increased.(3)These results indicate that exercise intervention before and after inducing diabetes can reverse/enhance the phosphoinositide 3-kinase-protein kinase B phosphorylation level in skeletal muscle,increase insulin sensitivity,improve lipid metabolism and disorder of glucose metabolism,and ultimately effectively improve and prevent the occurrence and development of type 2 diabetes.