罗格列酮改善胰岛素抵抗细胞摄取葡萄糖的途径研究

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10-5 mol/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.

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

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-gamma), 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.