罗格列酮促进AMPK蛋白磷酸化改善db/db小鼠胰岛素抵抗  

Rosiglitazone promotes phosphorylation of AMPK protein and improves insulin resistance in db/db mice

作　　者：胡娜[1] 袁琳[1] 方龙娟 姜逸 钟霄毓[1] 林敏[1] 陆敏[1] 孙银强[1] 陆雄[1] HU Na;YUAN Lin;FANG Long-juan;JIANG Yi;ZHONG Xiao-yu;LIN Min;LU Min;SUN Yin-qiang;LU Xiong(Science and Technology Experimental Center of Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学科技实验中心,上海201203

出　　处：《上海预防医学》2020年第8期646-650,共5页Shanghai Journal of Preventive Medicine

基　　金：上海市卫生和计划生育委员会项目(201540049);上海市市属博士学科点建设基金项目(B 201504);上海中医药大学预算内项目(2016YSN29);杏林中青年人才培养项目(A1-U17205010433)。

摘　　要：【目的】观察罗格列酮对2型糖尿病db/db小鼠肝脏、骨骼肌和脂肪中5′-单磷酸腺苷活化蛋白激酶(AMPK)和葡萄糖转运蛋白4(GLUT4)的蛋白表达的影响,了解罗格列酮调节AMPK信号通路的初步机制。【方法】将db/db小鼠按血糖浓度随机分层分为模型组和罗格列酮组;同窝出生的db/m小鼠为正常对照组。灌胃给药4周(罗格列酮5 mg/kg,其余组给予同等剂量的生理盐水),分别于用药2周和4周后检测小鼠的空腹血糖;用药4周末处死动物,立即取肝脏、皮下脂肪组织和腓肠肌,置于-80℃环境保存,用免疫印迹试验(Western blot)检测AMPK、p-AMPK以及GLUT4的蛋白表达。【结果】①罗格列酮显著降低db/db小鼠的空腹血糖浓度。用药2周后模型组血糖浓度为(22.09±3.67)mmol/L,罗格列酮组血糖浓度为(14.18±3.59)mmol/L(P<0.05);用药4周后模型组血糖浓度为(23.08±3.66)mmol/L,罗格列酮组血糖浓度为(14.18±3.59)mmol/L(P<0.01);②罗格列酮可上调db/db小鼠肝脏、骨骼肌和脂肪组织AMPK磷酸化水平,增加骨骼肌和脂肪组织的GLUT4蛋白含量。【结论】罗格列酮可增加db/db小鼠肝脏、肌肉和脂肪组织AMPK的磷酸化和GLUT4的蛋白表达,促进外周组织的葡萄糖摄取和利用,提示其可部分通过AMPK通路调节db/db小鼠的糖代谢。[Objective]To observe the effect of rosiglitazone on the protein expression of AMPK and GLUT4 in peripheral tissue(liver,skeletal muscle and fat)of type 2 diabetic db/db mice and to prove that rosiglitazone can regulate the glucose metabolism in db/db mice partly through the AMPK pathway.[Methods]db/db mice were randomly divided into model group and rosiglitazone group according to their blood glucose.The db/m mice were normal control group.After 4 weeks of administration,fasting blood glucose was detected in each group.Western blot was used to detect the contents of AMPK,p-AMPK and GLUT4 in liver,skeletal muscle and adipose tissue.[Results](1)Rosiglitazone significantly reduced the fasting blood glucose of db/db mice;(2)Rosiglitazone increased the level of AMPK phosphorylation in the liver,skeletal muscle and adipose tissue of db/db mice,and increased the content of GLUT4 protein in skeletal muscle and adipose tissue.[Conclusion]Rosiglitazone can increase the phosphorylation of AMPK and the expression of GLUT4 protein in the liver,muscle and fat tissue of db/db mice,and promote the uptake and utilization of glucose in peripheral tissue,suggesting that it can regulate glucose metabolism in db/db mice partly through the AMPK pathway.

关 键 词：罗格列酮 5′-单磷酸腺苷活化蛋白激酶(AMPK) 糖代谢 DB/DB小鼠 

分 类 号：R589.1[医药卫生—内分泌]