乙醇对大鼠骨骼肌胰岛素信号传递分子表达的影响  

Effects of alcohol feeding on the expression of insulin signal molecules in rats' skeletal muscle

作　　者：完强[1] 高聆[1] 刘毅[1] 王芙蓉[1] 任萌[1] 赵家军[1] 

机构地区：[1]山东大学山东省立医院,山东济南250021

出　　处：《毒理学杂志》2005年第1期35-37,共3页Journal of Toxicology

基　　金：山东省自然科学基金资助 (Y2 0 0 1C1 2 )

摘　　要：目的　探讨乙醇对大鼠骨骼肌葡萄糖摄取能力和胰岛素受体 (IR)、胰岛素受体底物 1(IRS1)和胰岛素受体底物 2 (IRS2 )及葡萄糖转运体 4(glut4)表达的影响。方法　雄性Wistar大鼠 2 0只 ,随机分为对照组和饮酒组 ,每组 10只。饮酒组每天乙醇灌胃 1次 ,乙醇量为 5g (kg·d) ;对照组每天蒸馏水灌胃 1次 ,蒸馏水量 5g (kg·d)。喂养时间 5个月。测大鼠空腹血糖和胰岛素、口服糖耐量 2h血糖 ;体外胰岛素刺激实验检测骨骼肌糖摄取能力 ;用RT- PCR和Westernblot法测定IR、IRS1和IRS2mRNA和蛋白表达水平 ,Real- timePCR测定glut4mRNA水平。结果　与对照组相比 :(1)饮酒组大鼠空腹血糖、空腹血胰岛素和口服糖耐量 2h血糖未见差异 ;(2 )饮酒组大鼠骨骼肌细胞基础和胰岛素刺激后糖摄取能力显著下降 (P <0 . 0 5 ) ;(3 )饮酒组大鼠骨骼肌glut4mRNA水平显著下降 (饮酒组 :△CT =5 . 3 7± 0 .2 4,对照组 :△CT =4. 86± 0 .3 1,P <0 .0 1) ;(4 )饮酒组大鼠骨骼肌IR、IRS1和IRS2mRNA及蛋白水平明显增加 (P <0 . 0 5 )。结论　长期摄入乙醇可以通过下调glut4表达而损害大鼠骨骼肌胰岛素敏感性 ,而胰岛素受体及其底物 1、2表达呈代偿性上调。Objective To investigate the effects of alcohol intake on the expres sion of insulin signal molecules in rats' skeletal muscle. Methods Twenty male Wistar rats were randomly divided into 2 groups and received either distilled w ater (control group) or alcohol (alcohol -fed group) for 5 months. Alcohol w as ad ministered using esophageal incubation with a single daily doses: 5 g/kg. Fastin g plasma glucose, fasting serum insulin and plasma glucose after oral glucose loa d 2h were measured. The ability of insulin-stimulated glucose uptake of skeleta l muscle cells was detected. The expression of insulin receptor (IR), insulin rec eptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) were quantified using RT-PCR and western blot. The mRNA level of glucose transporter 4(glut4)was also measured using real-time PCR. Results Compared with the control group, rats in alcohol-fed g roup: (1) showed no differences in fasting plasma glucose, fasting serum insulin and 2h plasma glucose levels after oral glucose load; (2) decreased basal and i nsulin-stimulated glucose uptake (P<0.05), indicating that alcohol might i mpair in sulin sensitivity; (3) decreased mRNA level of glut4 (alcohol-fed group:△CT=5.37±0.24,control group:△CT=4.86±0.31,P<0.01); (4) increased express ion of IR, IRS1 and IRS2, both at protein levels (P<0.05) and mRNA level ( P<0.05). Conclusion These data suggest alcohol intake might impair insulin sensitivity via down - regulating the expression of glut4, and such an effect is accompanied with the u p-regulated expression of IR, IRS1 and IRS2.

关 键 词：骨骼肌 分子表达 信号传递 胰岛素受体底物 Real-time Wistar大鼠 mRNA水平 glut4 Western 胰岛素刺激 葡萄糖转运体 RT-PCR 蛋白表达水平 胰岛素敏感性 空腹血糖 2H血糖 葡萄糖摄取 BLOT法 PCR测定 对照组 蒸馏水量 喂养时间 

分 类 号：R337[医药卫生—人体生理学] R392.12[医药卫生—基础医学]