运动通过增强大鼠Caveolin-3/eNOS信号转导缓解胰岛素抵抗形成的机制

Exercise intervention improves insulin resistance by enchancing Caveolin-3/eNOS in rats

目的:探讨Caveolin-3/e NOS信号转导在游泳运动改善高脂饮食大鼠胰岛素抵抗(IR)中的作用,为胰岛素抵抗及其并发症的防治提供理论依据。方法:以SD大鼠为实验对象,随机分为3组:正常对照组(C组)、高脂饮食组(H组)、高脂饮食运动组(HE组)。通过8周高脂饲料喂养建立IR大鼠动物模型,同时对大鼠实施无负重游泳运动干预。用正糖钳技术结合胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI)评价动物模型的建立;通过观察运动对高脂饮食IR大鼠骨骼肌e NOS和GLUT4含量,Caveolin3(Cav-3)m RNA的表达水平,p Akt Ser473和Akt蛋白表达的变化,探讨运动干预IR的机制。结果:(1)8周高脂饮食喂养后,H组大鼠葡萄糖输注速率(GIR)显著下降(P<0.01),ISI水平显著下降(P<0.01),HOMA-IR水平显著增加(P<0.01),提示胰岛素抵抗大鼠建模成功。(2)8周游泳干预后,与H组相比,HE组大鼠GIR显著增加(P<0.01),血清INS含量和HOMA-IR水平均显著降低(P<0.01),ISI水平显著增加(P<0.05或P<0.01);骨骼肌Cav-3 m RNA表达水平,p Akt Ser473和Akt蛋白表达水平均显著增加(P<0.05或P<0.01)。结论:8周游泳运动可通过上调骨骼肌Cav-3的表达水平,激活e NOS/Akt通路,从而增加GLUT4移位,缓解高脂饮食大鼠IR的形成。

Objective： To investigate the role of Caveolin-3/eNOS in swimming exercise-induced insulin resistance for high- fat-diet rats. Method： SD rats were randomly assigned to 4 groups： @Sedentary rats were fed with normal diet group （C group, n=10）.@Sedentary rats were fed with high-fat diet group （H group, n=9）.@High-fat diet rats were given 90rain/time swimming（HE group, n=10）. Rats of H group were fed with high-fat diet for 8 weeks to induce in- sulin resistance （IR）. 8 weeks later, the FBG, FINS, HOMA-IR, ISI and euglycemic-hyperinsulinemic clamp ex- periments were used to evaluate the animal model of IR and effects of exercise intervention. By observing the contents of skeletal muscle eNOS and GLUT4, the expression of Caveolin3 （Cav-3） mRNA, pAktSer473 and Akt, we explored the mechanism involved in the exercise-induced IR. Result： After 8-week exercise, in the HE group, the GIR was significantly increased （P〈0.01）, the levels of INS and HOMA-IR were dramatically decreased （P〈0.05）, the level of ISI was obviously increased （P〈0.01）,the expression of cav-3 mRNA, pAktSer473 and Akt were obviously increased （P〈0.01 or P〈0.05）, when com- pared with those in the H group. Conclusion： Swimming exercise can ameliorate high-fat-diet-induced skeletal muscle IR in rats through increas- ing caveolin 3/eNOS signaling transduction.