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学科主题基础医学
Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders
Song, Ruisheng1,2; Peng, Wei1; Zhang, Yan1; Lv, Fengxiang1; Wu, Hong-Kun1; Guo, Jiaojiao1; Cao, Yongxing3; Pi, Yanbin3; Zhang, Xin3; Jin, Li1; Zhang, Mao1; Jiang, Peng1; Liu, Fenghua1; Meng, Shaoshuai1; Zhang, Xiuqin1; Jiang, Ping1; Cao, Chun-Mei1; Xiao, Rui-Ping1,4
刊名NATURE
2013-02-21
DOI10.1038/nature11834
494期:7437页:375-379
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]SKELETAL-MUSCLE ; NEGATIVE REGULATOR ; DIABETES-MELLITUS ; RECEPTOR ; GLUCOSE ; OBESE ; DEGRADATION ; DYSFUNCTION ; RATS ; MICE
英文摘要

Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes(1). Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal(2,3), the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1); and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.

语种英语
WOS记录号WOS:000315312900043
项目编号2012CB518000 ; 2013CB531200 ; 2012CB944501 ; 81070674 ; 81070116 ; 3/22/002 ; 81130073
资助机构National Basic Research Program of China ; National Natural Science Foundation of China
引用统计
被引频次:99[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/400002259/53485
专题北京大学基础医学院_心血管所
北京大学第三临床医学院_运动医学研究所
北京大学临床肿瘤学院_人力资源处
作者单位1.Peking Univ, Ctr Life Sci, Beijing 100871, Peoples R China
2.Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
4.Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China
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GB/T 7714
Song, Ruisheng,Peng, Wei,Zhang, Yan,et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders[J]. NATURE,2013,494(7437):375-379.
APA Song, Ruisheng.,Peng, Wei.,Zhang, Yan.,Lv, Fengxiang.,Wu, Hong-Kun.,...&Xiao, Rui-Ping.(2013).Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders.NATURE,494(7437),375-379.
MLA Song, Ruisheng,et al."Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders".NATURE 494.7437(2013):375-379.
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