【作者】 陈小琳；

【导师】 毕会民；

【作者基本信息】 武汉大学 ， 内科学， 2004， 硕士

【摘要】 目的：研究高脂喂养的胰岛素抵抗大鼠骨骼肌细胞膜葡萄糖转运蛋白4(Glucose Transporter 4，GLUT4)的表达情况，探讨罗格列酮对胰岛素抵抗大鼠骨骼肌细胞葡萄糖转运蛋白4(GLUT4)转位的影响。 方法：将140-180g雄性SD(Sprague-Dawley)大鼠41只随机分为两组，正常对照组10只，高脂饲养实验组31只，8周后胰岛素抵抗大鼠造模成功。将高脂饲养大鼠随机分为未干预组(9只)、罗格列酮组(12只)、和饮食干预组(9只)，饮食干预组改为正常饲料喂养，余继续原来喂养，罗格列酮组加罗格列酮1mg／kg灌胃。4周后，大鼠均禁食12h皮下注射胰岛素10U／kg，15min后处死大鼠并取骨骼肌组织及内脏脂肪，应用Western-bloting印迹法分析骨骼肌细胞膜GLUT4表达量。同时检测空腹血糖(FPG)、空腹血浆胰岛素(FIN)和称量内脏脂肪重量。 结果：喂养8周后，结果显示高脂喂养组空腹血糖、空腹血浆胰岛素增高、ISI下降，与对照组比较有显著性差异(P＜0.001)，而体重(WEIGHT)无明显改变(P＞0.05)。干预4周后，罗格列酮组FPG与对照组和饮食治疗组FPG比较，无显著性差别(P＞0.05)，这三组FPG与高脂喂养组比较，均明显降低(P＜0.001)。罗格列酮组与饮食治疗组之间，FIN、Fat-weight、Fat／w(内脏脂肪与体重比)及ISI无显著性差别(P＞0.05)，与高脂喂养组比较，罗格列酮和饮食治疗组FIN、Fat-weight、Fat／w均显著性降低而ISI显著性增高(P＜0.001)，但FIN、Fat-weight、Fat／w均显著性高于正常对照组而ISI显著性降低(P＜0.001)。在胰岛素刺激下，胰岛素抵抗大鼠骨骼肌细胞膜GLUT4表达较正常大鼠下降52.72％(P＜0.001)，罗格列酮及饮食干预组，细胞膜GLUT4表达较未干预胰岛素抵抗大鼠分别增加49.53％、50.34％(P＜0.001)，与正常对照组之间无明显差异(P＞0.05)。 结论：高脂喂养可诱导正常SD大鼠产生胰岛素抵抗，胰岛素抵抗主要表现在胰岛素敏感组织骨骼肌细胞膜在胰岛素诱导下的GLUT4转位异常；罗格列酮可改善胰岛素刺激的GLUT4转位损害，从而改善高脂喂养所引起的骨骼肌组织胰岛素抵抗，并且这种作用与饮食干预同效。更多还原

【Abstract】 Objective: To investigate expression of glucose transporter 4 (GLUT4) in the cell membrane of skeletal muscle of high-fat-fed rats and effects of rosiglitazone on GLUT4 translocation to the plasma membrane in skeletal muscle of high-fat-fed rats .Methods: 41 male Sprague Dawley rats were randomized to receive high-fat (31) or standard chow diet (10) for 8 weeks, and feeding high-fat diet induced insulin resistance in skeletal muscle of rats. Consequently 30 high-fat-fed rats were randomized for treatment with rosiglitazone (1mg/kg), standard chow diet, or placebo (high-fat diet) in a 4 weeks trial. Overnight-fasted rats were injected with insulin (10units/kg) for 15 min. Isolated rats skeletal muscle was used for studying GLUT4 by Western blotting analysis. At the same time, plasma concentration of glucose, insulin, weight and viscero-fat were measured.Results: Feeding rats a high-fat diet for 8 weeks resulted in hyperinsulineemia, hyperglycemia, and loss of insulin sensitivity. It had significant difference (P<0.001) compared with chow-fed rats. But there had on change in weight of two groups (P>0.05). After intervention study for 4weeks, plasma concentration of insulin and weight of viscero-fat in rosiglitazone and standard chow diet groups were significantly lower than that of high-fat-fed rats, and insulin sensitive index was much higher (P<0.001). Insulin-stimulated translocation of GLUT4 to the plasma membrane in muscles of high fat-fed rats was significantly lower than that of standard chow-fed rats (52.72% P<0.001). But the defects were fully prevented by dietary rosiglitazone or standard chow diet (respectively 49.53%, 50.34%, P<0.001).Conclusion: High-fat diet-mediated insulin resistance is linked to defective insulin-stimulated translocation of GLUT4 glucose transporters to cell membrane of skeletal muscle. Rosiglitazone is an insulin-sensitizing agent that appears to prevent insulin resistance in skeletal muscle of high-fat-fed rats by selectively improving GLUT4 translocation to the plasma membrane, and the effect is equivalent to intervention of standard chow diet.更多还原