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罗格列酮改善胰岛素抵抗细胞摄取葡萄糖的途径研究

Mechanism of Rosiglitasone to Improve Glucose-uptake of 3T3-L1 Adipocyte with Insulin Resistance Induced by Dexamethasone and Insulin

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【作者】 杨桂枝; 高小平; 晏菊芳; 欧可群; 赵佳;

【Author】 YANG Gui-zhi,GAO Xiao-ping,YAN Ju-fang,OU Ke-qun,ZHAO Jia.Department of Histology,Embryology & Neurobiology,West China School of Preclinical and Forensic Medicine,Sichuan University,Chengdu 610041,China

【机构】 四川大学华西基础医学与法医学院组织胚胎学与神经生物学教研室; 地奥集团药物研究所; 四川大学华西基础医学与法医学院组织胚胎学与神经生物学教研室 成都610041; 成都610041;

【摘要】 目的探讨地塞米松和胰岛素联合作用诱导3T3-L1脂肪细胞产生胰岛素抵抗后,罗格列酮改善抗性细胞摄取葡萄糖的途径。方法在地塞米松和胰岛素诱导3T3-L1脂肪细胞产生胰岛素抵抗后,加入10-5mol/L罗格列酮,作用48 h改善细胞抗性,提取细胞总RNA和总蛋白,Western blot显示葡萄糖转运子(GLUT4)丰度,RT-PCR检测GLUT4和信号分子c-Cbl相关蛋白(c-Cbl associated protein,CAP)的基因表达。结果1罗格列酮显著增加了细胞GLUT4的转录水平和翻译水平,其表达丰度介于正常组与抵抗组之间。2罗格列酮提高了CAP基因水平,增强经CAP途径调节的GLUT4的转位。结论罗格列酮可能通过启动其下游基因GLUT4和CAP基因表达,增加GLUT4的数目,并激活CAP信号途径,提高GLUT4向细胞膜的转位,改善细胞对葡萄糖的摄取,从而改善胰岛素抵抗。

【Abstract】 Objective To study the mechanism of rosiglitasone to improve glucose-uptake of 3T3-L1 adipocyte with insulin resistance induced by dexamethasone and insulin.Methods Insulin resistance was induced to 3T3-L1 adipocyte after chronic treatment of dexamethasone and insulin.The insulin resisted 3T3-L1 adipocyte was treated with 10-5 mol/L of rosiglitasone for 48 h.The mRNA,protein of glucose transporter GLUT4 and CAP gene were then examined.Results ① Rosiglitasone increased the expression of GLUT4 mRNA and protein inhibited by dexamethasone and insulin although it had not reached a normal level.② Rosiglitasone increased the mRNA of CAP,which remained unchanged during insulin resistance.Conclusion Rosiglitasone,an insulin sensitizer,might up-regulate GLUT4 and CAP along with the peroxisome proliferators activated receptor gamma(PPAR-γ),which not only increases the GLUT4,but also activates the CAP-depended signaling pathway;improves the translocating of GLUT4 to the cell membrane;and increases the ability of glucose-uptake of cells.

  • 【文献出处】 四川大学学报(医学版) ,Journal of Sichuan University(Medical Science Edition) , 编辑部邮箱 ,2007年05期
  • 【分类号】R96
  • 【被引频次】11
  • 【下载频次】340
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