北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 期刊论文
学科主题: 基础医学
题名:
Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue
作者: Li, Yang1; Zhang, Heng1; Jiang, Changtao1; Xu, Mingjiang1; Pang, Yanli1; Feng, Juan1; Xiang, Xinxin1; Kong, Wei1; Xu, Guoheng1; Li, Yin1; Wang, Xian1
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2013-04-05
DOI: 10.1074/jbc.M112.431627
卷: 288, 期:14, 页:9583-9592
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: UNFOLDED PROTEIN RESPONSE ; ER STRESS ; ACCELERATED ATHEROSCLEROSIS ; MACROPHAGE POLARIZATION ; TRANSCRIPTION FACTOR ; QUALITY CONTROL ; MESSENGER-RNA ; JNK PATHWAY ; OBESITY ; HOMOCYSTEINE
英文摘要:

Type 2 diabetes is a chronic inflammatory metabolic disease, the key point being insulin resistance. Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of type 2 diabetes. Previously, we found that hyperhomocysteinemia (HHcy) induced insulin resistance in adipose tissue. Here, we hypothesized that HHcy induces ER stress, which in turn promotes insulin resistance. In the present study, the direct effect of Hcy on adipose ER stress was investigated by the use of primary rat adipocytes in vitro and mice with HHcy in vivo. The mechanism and the effect of G protein-coupled receptor 120 (GPR120) were also investigated. We found that phosphorylation or expression of variant ER stress markers was elevated in adipose tissue of HHcy mice. HHcy activated c-Jun N-terminal kinase (JNK), the downstream signal of ER stress in adipose tissue, and activated JNK participated in insulin resistance by inhibiting Akt activation. Furthermore, JNK activated c-Jun and p65, which in turn triggered the transcription of proinflammatory cytokines. Both in vivo and in vitro assays revealed that Hcy-promoted macrophage infiltration aggravated ER stress in adipose tissue. Chemical chaperones PBA and TUDCA could reverse Hcy-induced inflammation and restore insulin-stimulated glucose uptake and Akt activation. Activation of GPR120 reversed Hcy-induced JNK activation and prevented inflammation but not ER stress. Therefore, HHcy inhibited insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote proinflammatory cytokine production and facilitating macrophage infiltration. These findings reveal a new mechanism of HHcy in the pathogenesis of insulin resistance.

语种: 英语
所属项目编号: 81070683 ; 81121061 ; 31230035 ; 81170795 ; 30971085 ; 2011CB503904 ; 2010CB912504 ; NCET-10-0183 ; 7112080
项目资助者: National Natural Science Foundation of China ; Major National Basic Research Program of China ; Program for New Century Excellent Talents in University ; Beijing Natural Science Foundation
WOS记录号: WOS:000317114000002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51593
Appears in Collections:基础医学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 10091, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China

Recommended Citation:
Li, Yang,Zhang, Heng,Jiang, Changtao,et al. Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(14):9583-9592.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Li, Yang]'s Articles
[Zhang, Heng]'s Articles
[Jiang, Changtao]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Li, Yang]‘s Articles
[Zhang, Heng]‘s Articles
[Jiang, Changtao]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace