·糖尿病基础研究·

　　【摘 要】 目的 观察吡格列酮对高脂饮食诱导的胰岛素抵抗(IR)大鼠肝组织蛋白酪氨酸磷酸酸酶-1B(PTP-1B)、及胰岛素受体底物-2(IRS-2)表达的影响。 方法 将40只SD大鼠随机分为高脂饮食(HF)组30只和正常对照(NC)组10只和高脂饮食(HF)组30只，其中HF组又分为高脂对照(HFN)亚组15只和吡咯列酮(HFP)亚组,每组各15只;。喂养12周后，HFP组给予吡格列酮灌胃2周，并测定大鼠体重、FBGFPG、空腹胰岛素FIns、TG、TC、胰岛素敏感性IS;。应用免疫组化、免疫印迹、免疫沉淀技术检测肝组织 PTP-1B、及IRS-2的表达。 结果 免疫组化：PTP-1B表达HFN亚组较NC组显著增高(P<0.01)， HFP亚组较HFN亚组显著降低(P<0.01);免疫印迹：PTP-1B表达HFN、组和HFP亚组均明显高于NC组(P<0.01或P<0.05)，且HFP亚组明显低于亚HFN组(P<0.01);免疫沉淀：IRS-2磷酸化程度HFN亚组较NC组明显降低 (P<0.01)，HFP亚组较HFN亚组明显增高(P<0.05)。 结论 吡格列酮能够改善IR，其作用机制可能与抑制PTP-1B表达从而使胰岛素信号转导分子 IRS-2表达增强有关。

　　【关键词】 噻唑烷二酮类吡格列酮;胰岛素抗药性胰岛素抵抗;蛋白质酪氨酸磷酸酶蛋白酪氨酸磷酸酯酶-1B;受体, 胰岛素胰岛素受体底物-2;肝脏 肝脏

Effect of pioglitazone on the expressions of protein-tyrosine tyrosine-phosphatase -1B and insulin receptor substrate -2 in the liver of rats with insulin resistance induced by high-fat-diet ZHAO huiHui, YU suSu-guo, SUN jiJi-hua, et al. Binzhou Medical University Hospital, Binzhou 256603, China

Corresponding author: YU Su-guo, E-mail: yusuguo@sina.com

　　【Abstract】 Objective To observe the effect of pioglitazone on the expressions of protein tyrosine phosphatase 1B (PTP-1B) and insulin receptor substrate 2 (IRS-2) in the liver of rats with insulin resistance induced by high-fat-diet. Methods Forty SD rats were randomized into normal high fat diet group (HF), n=30, and normal control group (NC), n=10. The HF group was subdivided into HFN group and HFP group with 15 rats in each. Twelve weeks later, the HFP group was lavaged with pioglitazone for two weeks. The body weight, fasting blood glucose, fasting insulin (FIns), triglycerides (TG), total cholesterol (TC), and insulin sensitive index of this group were measured, and the expressions of PTP-1B and IRS-2 in the liver tissue were determined with immunohistochemistry, western-blotting, and immunoprecipitation. Results Immunohistochemistry: The PTP-1B expression in the HFN group was significantly increased compared with the NC group (1039.54±53.29 vs 856.37±33.26, P<0.01), and that in the HFP group was significantly decreased compared with the HFN group (920.62±85.34 vs 1039.54±53.29, P<0.01). Western-blotting: The PTP-1B expression in the HFN group and HFP group were all significantly increased compared with the NC group (HFN vs NC:157.7% vs 100%, P<0.01; HFP vs NC: 127.1% vs 100%, P<0.05), and that in the HFP group was significantly decreased compared with the HFN group (127.1% vs 157.7%, P <0.01). Immunoprecipitation: The IRS-2 phosphorylation of the HFN group was lowered compared with the NC group (53% vs 100%, P <0.01), and that of the HFP group was increased compared with the HFN group (78% vs 53%, P <0.05). Conclusion Pioglitazone improves insulin resistance, the mechanism of which is possibly related to the inhibited expression of PTP-1B and the enhanced expression of IRS-2.

　　【Key wordsWords】Thiazolidinediones; Insulin resistance; Protein Protein-tyrosine tyrosine-phosphatase (PTP)-1B; RInsulin receptor; Insulin; substrate-2;Liver