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学科主题基础医学
Long term liver specific glucokinase gene defect induced diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK
Li, Hui1; Wang, Xi1; Mao, Yiqing1; Hu, Ruobi1; Xu, Wei1; Lei, Zhen4; Zhou, Na1; Jin, Ling1; Guo, Tingting1; Li, Zhixin5; Irwin, David M.3; Niu, Gang2; Tan, Huanran1
关键词Liver-specific glucokinase knockout Diabetic cardiomyopathy Rosiglitazone Insulin receptor AMPK
刊名CARDIOVASCULAR DIABETOLOGY
2014-01-22
DOI10.1186/1475-2840-13-24
13
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Endocrinology & Metabolism
资助者National Natural Science Foundation of China (NSFC) ; National Key Technologies RD Program ; National Science Foundation of China - Canadian Institutes of Health Research (NSFC-CIHR) China-Canada Joint Health Research Initiative ; National Natural Science Foundation of China (NSFC) ; National Key Technologies RD Program ; National Science Foundation of China - Canadian Institutes of Health Research (NSFC-CIHR) China-Canada Joint Health Research Initiative
研究领域[WOS]Cardiovascular System & Cardiology ; Endocrinology & Metabolism
关键词[WOS]ACTIVATED PROTEIN-KINASE ; HOMEOSTASIS MODEL ASSESSMENT ; MOUSE MODEL ; MITOCHONDRIAL DYSFUNCTION ; MYOCARDIAL-INFARCTION ; MOLECULAR-MECHANISMS ; HEART-FAILURE ; MALONYL-COA ; RESISTANCE ; YOUNG
英文摘要

Background: The liver-specific glucokinase knockout (gck(w/-)) mouse experiences long-term hyperglycemia and insulin resistance. This study was designed to evaluate the functional and structural changes in the myocardium of 60 week-old gck(w/-) mice, and to investigate the effect of rosiglitazone on the myocardium in this model.

Methods: 60 week-old gck(w/-) mice were randomly divided into 3 groups: gck(w/-), gck(w/-) mice treated with insulin (1 U/kg) and gck(w/-) mice treated with rosiglitazone (18 mg/kg). Insulin or rosiglitazone treatment was for 4 weeks. Gck(w/w) litermates were used as controls. Echocardiography, electrocardiogram, biochemical, histopathological, ultrastructural, real time PCR and Western blot studies were performed to examine for structural and functional changes.

Results: Long-term liver-specific gck knockout in mice elicits hyperglycaemia and insulin resistance. Compared to age matched gck(w/w) mice, 60 week-old gck(w/-) mice showed decreased LV internal dimension, increased posterior wall thickness, lengthened PR and QRS intervals, up-regulated MLC2 protein expression, decreased SOD activity, increased MDA levels and up-regulated Cyba mRNA. Morphological studies revealed that there was an increase in the amount of PAS and Masson positively stained material, as did the number and proportion of the cell occupied by mitochondria in the gck(w/-) mice. Western blot analysis revealed that the levels of the insulin receptor, Akt, phosphorylated AMPK beta and phosphorylated ACC were reduced in gck(w/-) mice. These effects were partly attenuated or ablated by treatment with rosiglitazone.

Conclusions: Our results indicate that changes in the myocardium occur in the liver-specific glucokinase knockout mouse and suggest that reduced glucokinase expression in the liver may induce diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK protein levels. Rosiglitazone treatment may protect against diabetic cardiomyopathy by altering the levels of a set of proteins involved in cardiac damage.

语种英语
所属项目编号81102484 ; 30772603 ; 2006BAF07B01 ; 2009BAK61B01 ; 2009BAK61B04 ; 2012BAK25B01 ; 81061120525 ; CCI-109605
资助者National Natural Science Foundation of China (NSFC) ; National Key Technologies RD Program ; National Science Foundation of China - Canadian Institutes of Health Research (NSFC-CIHR) China-Canada Joint Health Research Initiative ; National Natural Science Foundation of China (NSFC) ; National Key Technologies RD Program ; National Science Foundation of China - Canadian Institutes of Health Research (NSFC-CIHR) China-Canada Joint Health Research Initiative
WOS记录号WOS:000332958800001
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60388
专题基础医学院_药理学系
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Beijing 100191, Peoples R China
2.Beijing N&N Genetech Co, Beijing, Peoples R China
3.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
4.Ningxia Med Univ, Dept Pharmacol, Yinchuan 750004, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Integrat Chinese & Western Med, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Li, Hui,Wang, Xi,Mao, Yiqing,et al. Long term liver specific glucokinase gene defect induced diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK[J]. CARDIOVASCULAR DIABETOLOGY,2014,13.
APA Li, Hui.,Wang, Xi.,Mao, Yiqing.,Hu, Ruobi.,Xu, Wei.,...&Tan, Huanran.(2014).Long term liver specific glucokinase gene defect induced diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK.CARDIOVASCULAR DIABETOLOGY,13.
MLA Li, Hui,et al."Long term liver specific glucokinase gene defect induced diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK".CARDIOVASCULAR DIABETOLOGY 13(2014).
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