胰岛素抵抗大鼠的肝脏中丝氨酸/酪氨酸磷酸化异常与血清TNF-α相关  

Serum TNF-α Is Correlated with the Abnormality of Serine/Tyrosine Phosphorylation of IRS-1 in the Liver of Insulin-Resistant Rats

作　　者：吴峰[1] 都健[1] 王慧敏[1] 裴丽娜[1] 王娟[2] 刘向阳[1] 关丽娜[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,辽宁沈阳110001 [2]山东曲阜市人民医院医保病房,山东曲阜273100

出　　处：《中国实验动物学报》2009年第5期360-363,共4页Acta Laboratorium Animalis Scientia Sinica

基　　金：辽宁省教育厅基金资助项目(编号:2008765)

摘　　要：目的探讨胰岛素抵抗大鼠胰岛素受体底物-1丝氨酸/酪氨酸磷酸化与肿瘤坏死因子α(TNF-α)的关系。方法雄性Wistar大鼠30只(体质量80~120 g),随机分为普通饮食组(NC)及高脂饮食组(FH)2组,每组15只。喂养10周,以高胰岛素-正常血糖钳夹技术评估胰岛素抵抗大鼠模型。应用ELISA法检测大鼠血清TNF-α含量,Western Blot法检测肝脏组织中胰岛素受体底物-1丝氨酸磷酸化(IRS-1Ser636)及酪氨酸磷酸化(IRS-1Tyr465)表达。结果FH组葡萄糖输注率(GIR)60-120水平明显低于NC组[(1.56±0.43 vs.5.15±0.66)mg/(kg.min),P<0.01];FH组大鼠TNF-αI、RS-1Ser636均高于NC组[(15.43±2.16 vs.5.4±2.16)pg/mL,P<0.01;(109.45±13.75 vs.94.23±15.05),P<0.05],IRS-1Tyr456水平低于NC组[(111.08±14.28 vs.125.77±14.51),P<0.05]。TNF-α水平与IRS-1Ser636呈正相关(r=0.503,P=0.024),与IRS-1Tyr465呈负相关(r=-0.521,P=0.019)。结论胰岛素抵抗大鼠TNF-α水平与IRS-1Tyr465负相关,与IRS-1Ser636正相关,提示TNF-α引起胰岛素抵抗机制可能与IRS-1磷酸化异常有关。Objective To investigate the relationship between TNF-α and abnormality of of serine/tyrosine phosphorylation of IRS-1 in insulin-resistant rats.Methods Thirty healthy male Wistar rats（weight between 80 to 120 g） were randomly divided into basic chow and high-fat diet groups,each group had 15 rats.Insulin-resistant rat models were assessed by hyperinsulinemia-euglycemia clamp technique after feeding high-fat diet for 10 weeks. TNF-α was detected by ELISA,and the expression of IRS-1Ser^（636）/IRS-1Tyr^（465） were measured by Western blot in livers.Results Compared with NC group,the glucose infusion rate（GIR） 60-120 in FH group was lower significantly [（1.56±0.43 vs.5.15±0.66） mg/（kg·min）,P0.01];the TNF-α,IRS-1Ser^（636） were higher significantly [（15.43±2.16 vs.5.4±2.16）pg/mL,P0.01;（109.45±13.75 vs.94.23±15.05）,P0.05],the level of IRS-1Tyr^（456） was lower [（111.08±14.28 vs.125.77±14.51）,P0.05].There was a positive correlation between TNF-α and IRS-1Ser^（636）（r=0.503,P=0.024） and negative correlation between TNF-α and IRS-1Tyr^（465）（r=-0.521,P=0.019）.Conclusion TNF-α has a negative correlation with IRS-1Tyr^（465）,positive correlation with IRS1Ser^（636） in insulin resistant rats,prompt that the mechanism of insulin resistance which was caused by TNF-α may have a relationship with the abnormality of IRS-1 phosphorylation.

关 键 词：胰岛素抵抗 胰岛素受体底物-1 肿瘤坏死因子Α 大鼠 

分 类 号：R587.1[医药卫生—内分泌]