【摘要】 目的探讨长期高脂饮食状态下不同剂量酒精摄入对大鼠胰岛素抵抗的影响及可能机制。方法清洁级Wistar大鼠,随机分为正常对照、高脂对照、高脂+5%、10%、20%、30%、40%酒精共7组。13w后,断头取血,测空腹血糖(FPG)及血胰岛素(FINS)浓度,计算胰岛素抵抗指数(homeostasis model assessment,HOMA-IR)及HOMA-β功能指数(HOMAβ-cellindex,HBCI)。RT-PCR法测定肝脏胰岛素受体底物-1(IRS-1),磷脂酰肌醇3激酶(PI-3K)、葡萄糖转运体-2(GLUT-2)的mRNA表达水平。Westernblotting测定肝脏PI-3K(p85α)、GLUT-2的蛋白表达水平。结果高脂对照组与正常对照组比,血胰岛素、HOMA-IR、HBCI明显升高(P<0.05),肝脏胰岛素信号传导关键分子没有显著差异。与高脂对照组比,高脂+酒精组空腹血糖、胰岛素抵抗指数明显升高(P<0.05),血胰岛素、胰岛β细胞功能指数明显下降(P<0.05);肝脏胰岛素信号传导关键分子mRNA、蛋白表达水平随酒精剂量的增加而逐渐下降。结论长期高脂饮食联合酒精摄入导致胰岛素抵抗;同时抑制肝脏胰岛素信号传导关键分子表达水平,在高剂量酒精组更明显,这可能是其导致胰岛素抵抗的分子机制。更多还原

【Abstract】 Objective To investigate the influence of different doses of alcohol intake with high-fat diet on insulin sensitivity and its molecular mechanisms in rats. Method Wistar rats were randomly assigned to two control groups (normal diet and high fat diet) and five test groups.The test groups were maintained on high fat diet and subjected to daily intragastric injections [10 ml/(kg bw.d)] containing different doses of alcohol (5%,10%,20%,30%,40%v/v). Body weight was measured once a week. The rats were sacrificed 13 weeks later,by decapitation to test the fasting blood glucose concentration (FPG) and blood insulin concentration (FINS),then insulin resistance index (homeostasis model assessment,HOMA-IR) and HOMA-β function index (HOMA β-cell index) were calculated. Total RNA from liver was isolated to test the mRNA expression of insulin receptor substrate-1 (IRS-1),phosphatidylinositol 3 kinase (PI-3K) and glucose transporter-2 (GLUT-2) by RT-PCR. Liver protein was isolated to test the protein expression of PI-3K (p85α) and GLUT-2 by Western blotting. Results FPG,FINS,HOMA-IR and HBCI were significantly increased in high-fat control group compared with normal control group (P<0.05),while the key molecules of insulin signal transduction in liver had no significant difference. FPG and HOMA-IR were significantly increased (P<0.05),while FINS and HBCI significantly decreased (P<0.05) in high-fat diet with alcohol group compared with high-fat diet control group. The mRNA and protein expression of the key molecules involved in insulin signaling in liver changed with alcohol decrease dose-dependently. Conclusion Chronic alcohol intake with high-fat diet resulted in insulin resistance and the decreased expression of the key molecules involved in insulin signaling in liver. The latter is probably the mechanism of insulin resistance induced by alcohol combined high-fat diet.更多还原