胰岛素抵抗细胞模型的胰岛素降解酶表达

　　【摘要】　目的　 了解胰岛素降解酶(IDE)基因、酶蛋白表达水平与胰岛素敏感性的关系，并初步探讨胰岛素 降解抑制剂氯喹改善胰岛素敏感性的分子机制。方法 　以原代大鼠肝细胞胰岛素抵抗(IR)模型为研究对象，分别采用免疫印迹技术和逆转录-聚 合酶链反应(RT-PCR)技术检测IR细胞模型的IDE酶蛋白表达(EIP)及基因表达水平(EIG)，同 时检测IDE　活性和反映细胞胰岛素敏感　性的14C-2-脱氧葡萄糖掺 入率及14C-醋酸盐掺入率，并观察氯喹对IR细胞模型上述指标的影响。结果IR细胞模型的EIG及EIP水平显著高于对照细胞，并与其IDE活 性呈显著正相关 ，与两种掺入率呈显著负相关。同时氯喹可明显抑制IR细胞模型以及对照 细胞的EIG 及EIP水平，而且抑制的程度与氯喹作用时间的长短密切相关。结论　大鼠肝细胞的EIG和EIP与其胰岛素敏感性之间呈负相关关系；高浓度胰岛 素可刺激大鼠肝细胞的IDE基因mRNA及酶蛋白的表达，而氯喹则对其起明显的抑制作用；胰 岛素和氯喹对大鼠肝细胞EIG的影响可能是通过影响IDE基因转录来实现。

Expression of insulin-degrading enzyme in insulin- resistance cell model

LI Chenzhong　ZHANG Suhua　SHU Chan gda　et al

　　（Department of Endocrinology,The First Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400016）

　　【Abstract】　Objective　To study the relationship among expression of insulin-degrading enzyme (IDE ) gene (EIG), enzyme protein and insulin sensitivity, and to investigate the mol ecular mechanism for improvement of insulin sensitivity by chloroquine. Methods　Expression of IDE protein (EIP) and EIG were de termi ned on insulin-resistance (IR) hepatocytes of rat by immunoblotting technique a nd RT-PCR respectively. Incorporation rate of 14　　C-2-d eoxyglucose and 14　　C-acetate which were used to estimate insulin sensitivity of cells, and IDE activity were determined in IR hepatocyte s of rat. Moreover, effects of chloroquine on these indices were observed. Results　EIG, EIP in IR cells were higher than those in the control cells. EIG and EIP were positively correlated with IDE activity, and negatively correlated with the two kinds of incorporation rate. Chloroquine significantly decreased EIG and EIP in IR cells and control cells, and the decr eases in EIG and EIP were correlated with the duration of treatment. Conclusion　EIG and EIP of rat hepatocytes were negatively c orrelated with insulin sensitivity; EIG and EIP of rat hepatocytes can be stimul ated with insulin at high concentration and inhibited with chloroquine; Effects of ins

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