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

关键词：胰岛素抵抗  运动  小窝蛋白3  内皮型一氧化氮合酶  2型糖尿病

Keywords:insulin resistance  exercise  caveolin 3  eNOS  type 2 diabetes mellitus

摘要：

      摘要 目的：探讨Caveolin-3/eNOS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eNOS和GLUT4含量, Caveolin3 (Cav-3) mRNA 的表达水平，pAktSer473和Akt蛋白表达的变化，探讨运动干预IR的机制。 结果：①8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。②8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 mRNA表达水平，pAktSer473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eNOS/Akt通路，从而增加GLUT4移位，缓解高脂饮食大鼠IR的形成。

Abstract:

      Abstract 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: ①Sedentary rats were fed with normal diet group (C group, n=10).②Sedentary rats were fed with high-fat diet group (H group, n=9).③High-fat diet rats were given 90min/time swimming(HE group, n=10). Rats of H group were fed with high-fat diet for 8 weeks to induce insulin resistance (IR). 8 weeks later, the FBG, FINS, HOMA-IR, ISI and euglycemic-hyperinsulinemic clamp experiments 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 compared with those in the H group. Conclusion: Swimming exercise can ameliorate high-fat-diet-induced skeletal muscle IR in rats through increasing caveolin 3/eNOS signaling transduction.