运动对胰岛素抵抗大鼠丝氨酸/酪氨酸磷酸化通路干预效应的研究  

Effect of exercise on phosphorylation of serine^(307)/tyrosine in insulin-resistant rats

作　　者：关丽娜[1] 都健[1] 王慧敏[1] 裴丽娜[1] 王娟[2] 吴峰[1] 刘向阳[1] 林志楠[1] 

机构地区：[1]中国医科大学第一临床医院内分泌科,沈阳市110001 [2]山东省曲阜市人民医院医保病房

出　　处：《中国糖尿病杂志》2010年第5期330-333,共4页Chinese Journal of Diabetes

基　　金：辽宁省教育厅基金资助项目(2008765)

摘　　要：目的观察运动对高脂膳食诱导胰岛素抵抗(IR)大鼠骨骼肌胰岛素受体底物1(IRS 1)丝氨酸^(307)(Ser^(307))磷酸化和酪氨酸(Tyr)磷酸化通路的影响。方法 Wistar大鼠75只,分为正常对照(NC)组、高脂膳食(HF)组。10周后再将HF组分为高脂膳食运动(HFE)组和高脂膳食非运动(HFNE)组。以钳夹技术观察各组大鼠胰岛素敏感性(IS)变化,Western Blot法检测大鼠骨骼肌IRS-1 Ser^(307)磷酸化和Tyr磷酸化水平。结果 (1)10周后HF组葡萄糖输注率(GIR_(60～120))明显低于NC组;与NC组比较,HF组IRS-1 Tyr磷酸化水平降低,IRS-1 Ser^(307)磷酸化水平升高(P均<0.01)。(2)14周后HFE组GIR_(60～120)明显高于HFNE组;与HFNE组比较,HFE组IRS-1 Tyr磷酸化水平升高,IRS-1 Ser^(307)磷酸化水平降低(P均<0.01)。结论运动干预改善IR大鼠IS,其机制可能与改善IRS-1 Ser^(307)/Tyr异常磷酸化有关。Objective To investigate the effect of swimming exercise on insulin receptor substrate-1 （IRS-1） phosphorylation in skeletal muscle of insulin-resistant rats. Methods Wistar rats were randomly assigned to normal control group （NC） and high-fat-diet group（HF）. 10 weeks later, HF group was divided into high-fat-diet feeding with （HFE group） and without （HFNE group） exercise. The insulin sensitivity in each group was assessed by eulgycemic-hyerinsulinemic clamp technique. Western blot was used to examine the contents of serin307 phosphorylation and tyrosine phosphorylation of IRS-1 protein in the skeletal muscle. Results 10 weeks later,the glucose infusion rate at 60 to 120 minutes （GIR60-120） was lower in HF group than in NC group 1-（1.56±0. 43）vs（5. 15±0.66） mg . kg- 1 . min-1 ,P〈0. 01]. As compared with NC group, the tyrosine-phosphorylation of IRS-1 was decreased in HF group （P〈 0.01） ,inversely the serine307 phosphorylated IRS-1 was increased in HF group（P〈0.01）. 14 weeks later, the GIR60-120 was higher in HFE group than in HFNE group[（4. 76±0.53）vs（1. 38±0.46） mg. kg -1 . min-1 ,P〈 0.01]. As compared with HFNE group, the tyrosine-phosphorylated IRS-1 was increased in HFE group（P〈0.01）, inversely the serine307 phosphorylated IRS-1 was decreased in HFE group （P〈 0.01）. The GIR60-120 was lower in HFE group than in NC group[（4.76±0.53）vs（5.28±0.58） mg. kg.1 min-1, P〈0.01]. There was statistical significant difference between NC and HFE group in serine307/ tyrosine phosphorylation of IRS-1 （P〈 0.01 ）. Conclusions Exercise can improve insulin sensitivity in insulin-resistant rats,which is partly due to the improvement of abnormal phosphorylation of serine307/ tyrosine in IRS-1.

关 键 词：运动 胰岛素抵抗 大鼠 丝氨酸磷酸化 酪氨酸磷酸化 

分 类 号：R587[医药卫生—内分泌]