有氧运动和膳食控制对2型糖尿病大鼠骨骼肌InsR-PI3K-GLUT4信号通路的影响

Effects of Aerobic Exercise and Dietary Control on InsR-PI3K-Glut4 Signaling Pathway in Skeletal Muscle of Rats with Type 2 Diabetes

目的:研究有氧运动和膳食控制对2型糖尿病(T2DM)大鼠骨骼肌InsR-PI3K-GLUT4信号通路的影响。方法:雄性SD大鼠62只,随机抽取8只作为对照组(C组,n=8),喂以标准普通饲料。其余54只在喂饲高脂膳食基础上,腹腔注射小剂量STZ建立糖尿病模型。然后随机分成糖尿病对照组(DM,n=9)、DM+运动锻炼组(DME,n=10)、DM+膳食控制组(DMD,n=10)、DM+运动锻炼+膳食控制组(DMED,n=10)4组。DM组大鼠继续喂饲高脂饲料,不进行运动锻炼;运动锻炼采用每天60min无负重游泳运动,每周6次;膳食控制喂饲与DM组等量的标准普通饲料。12周后,检测各组大鼠骨骼肌InsR亲和力以及PI3K和GLUT4含量。结果:(1)DM组骨骼肌GLUT4和PI3K含量显著低于C组(P<0.01,P<0.05);通过双因素方差分析,有氧运动显著增加T2DM大鼠PI3K含量(P<0.01),GLUT4含量增加无显著性差异(P>0.05);单纯膳食控制对增加T2DM大鼠GLUT4和PI3K含量均无显著性影响(P>0.05);运动和膳食控制对增加T2DM大鼠PI3K含量无显著交互作用(P>0.05),但对增加GLUT4含量有显著交互作用(P<0.05)。(2)DM组大鼠骨骼肌InsR高、低亲和力受体常数KD1、KD2和高、低亲和力受体结合容量RT1、RT2显著高于C组(P<0.01,P<0.05);通过双因素方差分析,有氧运动可显著降低T2DM大鼠KD2和RT1(P<0.01,P<0.05),但对降低KD1和RT2无显著性(P>0.05);膳食控制对KD1、KD2、RT1和RT2均无显著影响(P>0.05),有氧运动和膳食控制对KD1、KD2、RT1和RT2均无显著交互作用(P>0.05)。结论:(1)骨骼肌InsR结合力下降及其受体后PI3K作用的下调,导致骨骼肌GLUT4含量下降可能是T2DM发生的重要机制。(2)长期有氧运动通过提高T2DM大鼠骨骼肌InsR亲和力及其受体后PI3K的作用,增加骨骼肌GLUT4含量。单纯膳食控制对T2DM大鼠骨骼肌InsR亲和力和PI3K含量无显著影响。运动与膳食控制对改善T2DM大鼠InsR-PI3K-GLUT4信号通路无显著的交互作用。

Objective To research the effects of exercise and dietary control on InsR-PI3K-Glut4 in skeletal muscle of rats with type 2 diabetes mellitus （T2DM）. Methods 8 rats were randomly selected asnormal control group （C ,n = 8） from 62 male SD rats fed with standard diet. The remaining 54 were intraperitoneally injected small doses of streptozotocin on the basis of feeding high fat diet to establish T2DM animal models. Then T2DM rats were randomly divided into 4 groups：DM group （DM,n = 9）, DM＋exercise group （DME,n = 10）,DM＋diet control group （DMD,n = 10）,DM＋exercise＋diet control group（DMED,n = 10）. The rats in group DM continued feeding with high fat diet without exercise. Rats in groups DME and DMED swam 60 minutes per day,6 times a week,for a total of 12 weeks.Rats in diet consumed the same amount of feed as the rats in group DM. The glucose transporter 4 （GLUT4） and phosphatidylinositol 3 kinase （PI3K） concentrations,and the affinity of insulin receptor （InsR） in gastrocnemius were measured. Results（ 1 ）The GLUT4 and PI3K contents of skeletal muscle in group DM were significantly lower than those in group C （P 〈 0.01 ,P 〈 0.05）. PI3K content of skeletal muscle increased significantly （P 〈 0.01）,while the GLUT4 content remained unchanged （P 〉 0.05） in T2DM rats. GLUT4 and PI3K content in group DMD increased insignificantly （P 〉 0.05）. GLUT4 content increased significantly （P 〈 0.05） and PI3K content remained unchanged in group DMED（P 〉 0.05）. （2） The insulin receptor affinity constant KD1 and KD2, and insulin receptor binding capacity RT1 and RT2 in group DM were significantly higher than those in group C （P 〈 0.01 ,P 〈 0.05）. The KD1 and RT2 in group DMED decreased significantly （P 〈 0.01 ,P 〈 0.05）. The KD1,KD2,RT1 and RT2 either in group DME or DMED changed insignificantly （P 〉 0.05）. Conclusion （1）The decrease in insulin receptor affinity and down-regulation of PI3K in skeletal muscle caused decrease in GLUT4 content, which could be the important mechanism for the occurrence of type 2 diabetes. （2）Long-term aerobic exercise could increase GLUT4 content in skeletal muscle through improving insulin receptor affinity and PI3K,and such effect could not be seen in the rats with dietary control alone.