双脱甲氧基姜黄素对db/db小鼠胰岛素抵抗和糖稳态作用及机制研究  

Effectandmechanismof BDMC on insulin resistance and glucose homeostasis in db/db mice

作　　者：胡淑芳[1] 杨丽[1] 徐子辉 HU Shufang;YANG Li;XU Zihui(Department of Endocrine,Hankou Hospital of Wuhan,Wuhan 430012,China)

机构地区：[1]武汉市汉口医院内分泌科,武汉430012 [2]华中科技大学同济医学院附属武汉中心医院内分泌科,分子诊断湖北省重点实验室,武汉430014

出　　处：《实用医学杂志》2018年第22期3685-3689,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金青年项目(编号:31400916);武汉市卫生计生委项目(编号:WX15D39).

摘　　要：目的探讨双脱甲氧基姜黄素(BDMC)对db/db小鼠发生2型糖尿病(T2D)的作用及机制。方法 4周龄的db/db小鼠均衡随机分组为:db/db组、RG组和BDMC组,以C57BL/6为WT对照组。于每周检测空腹血糖,6周末置于监测其呼吸交换率和能量消耗变化,检测糖化血红蛋白、胰岛素、血脂含量,行口服糖耐量试验,计算胰岛素抵抗的稳态指数和定量胰岛素敏感性检测指数,Western blot检测肝脏G6Pase、PEPCK和骨骼肌p-AMPK、AMPK、PM-GLUT4、GLUT4、pAS160、AS160蛋白表达水平。结果 BDMC明显下调db/db小鼠升高的体质量、饮食、饮水量和空腹血糖,上调db/db小鼠降低的呼吸交换比率和能量消耗量,且比RG作用更明显;BDMC对db/db小鼠升高的外周血糖化血红蛋白无显著作用,但RG组下调含量;BDMC上调db/db小鼠降低的胰岛素敏感性,下调db/db小鼠升高的血浆胰岛素、胰岛素抵抗的稳态指数和定量胰岛素敏感性检测指数;BDMC下调db/db小鼠升高的TG、TC、LDL-C、HDL-C和FFA;BDMC下调db/db小鼠肝脏高表达的G6Pase和PEPCK蛋白,且优于RG;BDMC上调db/db小鼠骨骼肌低表达的p-AMPK、PM-GLUT4和pAS160蛋白,与RG效应没有明显的差异。结论 BDMC可明显上调骨骼肌AMPK-AS160-GLUT4信号通路及下调肝脏G6Pase和PEPCK减低糖再生,改善db/db小鼠胰岛素抵抗和糖脂代谢减慢,且优于罗格列酮。Objective To investigate the effect of bisdemethoxycurcumin(BDMC)on type 2 diabetes mel-litus(T2D)in db/db mice and its mechanism.Methods Four-week old db/db mice were randomly divided into db/db group,RG group and BDMC group,with C57BL/6 as WT group.Fasting blood glucose was detected weekly,and the respiratory exchange rate and energy expenditure were monitored.Plasma lipid concentrations,glycated hemoglobin(HbA1c)and insulin were detected.Oral glucose tolerance test(OGTT)was performed;the homeo-static index of insulin resistance(HOMA-IR)and quantitative insulin sensitivity check index(QUICKI)were cal-culated and western blot was used to detect the expression levels of G6Pase,PEPCK in liver and p-AMPK,AMPK,PM-GLUT4,GLUT4,pAS160 and AS160 in skeletal muscle.Results BDMC significantly lowered the body weight,food intake,water intake and fasting blood glucose of db/db mice and up-regulated the decreased respiratory exchange rate and energy expenditure in db/db mice,and the effect of BDMC was more obvious than that of RG.There was no significant effect of BDMC on blood glycemic hemoglobin(HbA1c),but RG down-regu-lated high level of HbA1c in db/db mice,obviously;BDMC improved insulin sensitivity of the db/db mice and reduced the plasma insulin,the homeostasis index of insulin resistance(HOMA-IR)and the insulin sensitivity index(QUICKI),TG,TC,LDL-C,HDL-C and FFA contents in db/db mice.BDMC reduced the content of G6Pase and PEPCK in liver of db/db mice significantly,and the effect of BDMC was more obvious than that of RG;BDMC improved the expression of p-AMPK,PM-GLUT4 and pAS160 in skeletal muscle of db/db mice,butthere was no significant difference when compared the effect of BDMC to that of RG.Conclusion BDMC obviously activates AMPK-AS160-GLUT4 signaling pathway in skeletal muscle,inactivates G6Pase and PEPCK-mediated gluconeogen-esis in liver and results in decreasing insulin resistance but increasing glycolipid metabolism in db/db mice,and its effect is superior to that of RG.

关 键 词：双脱甲氧基姜黄素 糖尿病 胰岛素抵抗 糖稳态 AMPK信号通路 

分 类 号：R587.1[医药卫生—内分泌]