二甲双胍对高脂饮食诱导的胰岛素抵抗大鼠LPIN1表达及AMPK通路的作用  

Influence of metformin on LPIN1 expression and AMPK signaling in high-fat diet-induced insulin resistant rats

作　　者：庄向华[1] 刘元涛[1] 倪一虹[1] 孙福敦[1] 陈诗鸿[1] 

机构地区：[1]山东大学第二医院内分泌科,山东济南250033

出　　处：《中国病理生理杂志》2011年第12期2276-2280,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81070641);山东省自然科学基金资助项目(No.Y2006C119)

摘　　要：目的:观察腺苷酸活化蛋白激酶(AMPK)激动剂二甲双胍对高脂饮食诱导的胰岛素抵抗大鼠LPIN1表达和AMPK通路的影响,探讨LPIN1在肝脏胰岛素抵抗中的可能作用机制。方法:将36只4周龄雄性Wistar大鼠随机分为2组:(1)对照组(Con)12只;(2)高脂饮食组(HF)24只。8周后高脂组再随机分为高脂(HF)组和二甲双胍干预(MET)组,继续喂养8周。测定肝脏甘油三酯和胆固醇水平,应用高胰岛素-正常葡萄糖钳夹技术测得葡萄糖输注率,以评价胰岛素敏感性。RT-PCR检测LPIN1、AMPKα1和AMPKα2 mRNA表达,Western blotting方法检测LPIN1、AMPKα1、AMPKα2和p-AMPKα蛋白表达。结果:HF组大鼠空腹血糖、胰岛素、血清以及肝脏中甘油三酯、胆固醇水平均高于Con组;二甲双胍干预后上述指标下降;HF组葡萄糖输注率低于Con组(P<0.01),MET组高于HF组(P<0.05)。3组大鼠肝脏AMPKαl、AMPKα2 mRNA和蛋白表达无显著差异(P>0.05);HF组大鼠肝组织p-AMPKα和LPIN1蛋白表达低于Con组(P<0.01),MET组高于HF组(P<0.01)。结论:高脂饮食导致大鼠胰岛素抵抗,AMPKα活性及LPIN1表达降低,应用二甲双胍干预后AMPKα活性以及LPIN1表达均增加,LPIN1和AMPK信号通路之间可能存在相互作用。AIM： To explore the regulatory mechanism of LPIN1 in hepatic insulin resistance by investigating the influence of metformin on the expression of LPIN1 and AMP-activated protein kinase（AMPK） signaling in the rats with high-fat diet-induced insulin resistance.METHODS： Thirty-six 4-week-old male Wistar rats were randomly divided into 2 groups： control group and high-fat diet（HF） group.The rats in HF group were fed with high-fat diet for 8 weeks and then were randomly divided into 2 subgroups： HF group and metformin intervention group,and the animals were continuously raised for 8 months.The mRNA levels of α1 and α2 subunit of AMPK as well as LPIN1 were measured by real-time RT-PCR.Phospho-AMPKα（Thr-172） was detected by Western blotting to evaluate the activity of AMPK.RESULTS： After 4 months,the rats in HF group showed significant increase in the levels of body weight,fast plasma glucose and insulin,and the levels of triglyceride and total cholesterol significantly elevated.Significant decrease in LPIN1 and phospho-AMPKα（Thr-172） expression in the rat livers were also observed.After treated with metformin,the metabolic indexes of the HF rats were improved.The mRNA and protein expression of AMPKα1 and AMPKα2 had no significant difference among the 3 groups.Metformin treatment also increased the expression of LPIN1 in the liver tissues of HF rats.CONCLUSION： The decrease in LPIN1 expression and AMPK activity may contribute to hepatic insulin resistance in diet-induced obese rats.Metformin improves the LPIN1 expression and AMPK activity through the interaction between LPIN1 and AMPK signal pathways.

关 键 词：胰岛素抵抗 AMP活化蛋白激酶 LPIN1蛋白 

分 类 号：R363[医药卫生—病理学]