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学科主题: 基础医学
题名:
Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders
作者: 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
发表日期: 2013-02-21
DOI: 10.1038/nature11834
卷: 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
所属项目编号: 2012CB518000 ; 2013CB531200 ; 2012CB944501 ; 81070674 ; 81070116 ; 3/22/002 ; 81130073
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000315312900043
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53485
Appears in Collections:基础医学院_心血管所_期刊论文

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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

Recommended Citation:
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.
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