Caveolin-3在白藜芦醇改善高脂诱导骨骼肌胰岛素抵抗中的作用

摘要

[Objective] In the high-fat-induced insulin resistance rat model, the role of caveolin-3 (CAV-3) in the effect of resveratrol (RSV) on insulin resistance in skeletal muscles was studied. [Methods] Rats were divided into three groups; normal diet group (NORM), high-fat diet group (HFD ), high-fat diet plus resveratrol group (HFD + RSV). The protective effect of resveratrol on insulin resistance were studied by measuring fasting glucose, fasting serum insulin, insulin sensitive index (ISI), intraperitoneal glucose tolerance test, and 2-deoxy-[3H] glucose uptake in vitro soleus muscles. Expression of caveolin-3 (CAV-3) and glucose transporter 4 (GLUT4) in the above processes were measured by Western blot analysis. [Results] RSV has protective effect on high-fat diet-induced insulin resistance. RSV elevated insulin-stimulated glucose uptake in isolated soleus muscle in vitro by enhancing GLUT4 translocation to the plasma membrane rather than increasing GLUT4 protein expression. RSV increased CAV-3 protein expression, which contributed to GLUT4 translocation. [Conclusion] The results showed that RSV ameliorates insulin resistance by increasing glucose uptake in skeletal muscles through a CAV-3-dependent pathway, and the mechanism was that RSV up regulates CAV-3 protein expression and enhances GLUT4 translocation to plasma membrane.%[目的]在高脂诱导的胰岛素抵抗大鼠模型上,探讨微囊蛋白3(CAV-3)在白藜芦醇改善骨骼肌胰岛素抵抗中的作用及机制.[方法]实验大鼠分3组:正常饮食组(NORM),高脂饮食组(HFD),高脂饮食加白藜芦醇干预组(HFD+ RSV).通过空腹血糖、胰岛素浓度、计算胰岛素敏感指数、腹腔葡萄糖耐量试验以及2-脱氧-[3H]葡萄糖的摄取,从整体上探讨白藜芦醇对胰岛素抵抗的保护作用.再通过免疫印迹检验微囊蛋白3(CAV-3)与葡萄糖转运蛋白4(GLUT4)在以上过程中的表达情况.[结果]HFD能显著诱导胰岛素抵抗,补充RSV能抑制高脂的诱导作用.离体骨骼肌实验证实,RSV的保护作用与其促进胰岛素诱导的葡萄糖摄取有关.免疫印迹证实RSV能够增加骨骼肌CAV-3蛋白表达,促进GLUT4向细胞膜的转运.[结论]白藜芦醇能改善高脂诱导的胰岛素抵抗,其保护作用与其上调CAV-3蛋白表达,促进GLUT4向细胞膜转运,改善骨骼肌葡萄糖的摄取有关.