Cardiac insulin resistance and microRNA modulators.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2011-07-31 DOI:10.1155/2012/654904
Lakshmi Pulakat, Annayya R Aroor, Rukhsana Gul, James R Sowers
{"title":"Cardiac insulin resistance and microRNA modulators.","authors":"Lakshmi Pulakat,&nbsp;Annayya R Aroor,&nbsp;Rukhsana Gul,&nbsp;James R Sowers","doi":"10.1155/2012/654904","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS), and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS) and angiotensin II (Ang II) activate mammalian target for rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2), it also renders cardioprotection via increased Ang II receptor 2 (AT2R) upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO) rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"654904"},"PeriodicalIF":0.0000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/654904","citationCount":"27","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Diabetes Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2012/654904","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2011/7/31 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 27

Abstract

Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS), and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS) and angiotensin II (Ang II) activate mammalian target for rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2), it also renders cardioprotection via increased Ang II receptor 2 (AT2R) upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO) rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

Abstract Image

Abstract Image

Abstract Image

心脏胰岛素抵抗和microRNA调节剂。
心脏胰岛素抵抗是一种代谢和功能障碍,通常与肥胖和/或心肾代谢综合征(CRS)有关,这种疾病可能因长期饮酒而加重。在营养过度的情况下,胰岛素(INS)和血管紧张素II (Ang II)的增加激活了哺乳动物雷帕霉素(mTOR)/p70 S6激酶(S6K1)信号传导的靶点,而慢性酒精消耗抑制了心脏组织中mTOR/S6K1的激活。虽然mTOR/S6K1的过度激活通过INS受体底物(IRS-1/2)的丝氨酸磷酸化诱导心脏INS抵抗,但它也通过增加Ang II受体2 (AT2R)上调和适应性肥大来实现心脏保护。在胰岛素抵抗和高胰岛素血症的Zucker肥胖(ZO)大鼠(CRS的啮齿动物模型)中,心脏组织中mTOR/S6K1信号的激活受保护性反馈机制的调节,该机制涉及mTOR↔AT2R信号回路和靶向S6K1的microRNA的廓形变化。这种调节可能在减轻进行性心力衰竭中起作用。相反,酒精介导的mTOR/S6K1的抑制,INS受体和生长抑制mir-200家族的下调,以及促进胎儿基因程序的mir-212的上调可能会加重crs相关的心肌病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
自引率
0.00%
发文量
0
审稿时长
3-8 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信