高脂饮食诱导的肥胖大鼠胰腺蛋白酪氨酸磷酸酶1B表达增高  

Increased expression of protein tyrosine phosphatase 1B in pancreas of high fat diet-induced obese rats

作　　者：张丽娟[1] 邹大进[1] 顾萍[1] 吴捷[1] 张征[1] 

机构地区：[1]上海第二军医大学附属长海医院内分泌科,上海松江区中心医院内分泌科200433

出　　处：《中华内分泌代谢杂志》2007年第5期437-441,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家"十五"攻关基金(2001BA70B01)

摘　　要：目的观察高脂饮食诱导的肥胖大鼠胰腺中蛋白酪氨酸磷酸酶1B(PTP-1B)的表达。方法选取SD大鼠20只,随机分为正常对照组10只,给予常规饲料;肥胖模型组10只,给予高脂饲料,共喂养12周。测定大鼠空腹胰岛素、血糖、甘油三酯、总胆固醇,附睾脂肪垫重量;观察肝脏形态学改变;进行葡萄糖耐量试验和胰岛素释放试验;用免疫组化和蛋白印迹法检测大鼠胰腺组织中PTP-1B蛋白的表达。用免疫沉淀法检测胰岛素受体(IR)和胰岛素受体底物1(IRS-1)磷酸化程度。结果(1)肥胖组胰岛素敏感指数显著低于对照组(0.36±0.18 vs 0.91±0.28,P<0.05);(2)肥胖组大鼠葡萄糖耐量受损,葡萄糖刺激的胰岛素Ⅰ相分泌反应受损;(3)肥胖组大鼠胰腺中PTP-1B蛋白与对照组相比,含量增加86%(P<0.01)。肥胖组胰腺中胰岛素诱导的IR和IRS-1磷酸化程度都降低。结论高脂饮食诱导的肥胖大鼠胰腺中PTP-1B蛋白表达量升高,从而使胰岛素诱导的IR和IRS-1磷酸化程度降低,可能是肥胖状态下引发胰岛产生胰岛素抵抗的机制之一。Objective To investigate the expression of protein tyrosine phosphatase （PTP） 1B in pancreas of obese rats induced by high fat diet. Methods Twenty male SD rats were randomly divided into control group on regular diet （n = 10）, and obesity model group on high fat diet （ n = 10）. After twelve weeks, fasting serum insulin, blood glucose, triglyceride, total cholesterol, epididymal fat weight were measured and the histomorphological change in liver were observed; glucose tolerance test and insulin releasing test were performed; The protein expression of PTP-1B in pancreas of rats was determined with Western blotting and immunohistochemistry. The phosphorylation of insulin receptor substrate-1 （ IRS-1 ） and insulin receptor （IR） were detected by immuno-precipitation. Results （ 1 ） The insulin sensitive index was significantly decreased in the high-fat-diet rats compared with the normal rats （0.36 ±0. 18 vs 0. 91 ±0.28,P 〈0.05）. （2） In obese rats, glucose tolerance and the acute first-phase insulin secretory response to glucose were impaired. （3）The protein levels of PTP-1B in pancreas of obesity rats was significantly increased by 86% compared with the control group （ P 〈0.01 ）. Insulin-stimulated IR and IRS-1 phosphorylation in the pancreas were reduced in the obese rats. Conclusion The increased PTP-1B level and the reduced insulin-stimulated IR and IRS-1 phosphorylations in pancreas seem to play an important role in the pathogenesis of islet insulin resistance induced by high fat diet.

关 键 词：蛋白酪氨酸磷酸酶1B 胰腺 胰岛素抵抗 

分 类 号：R589.2[医药卫生—内分泌] R587.1[医药卫生—内科学]