Cardiac Insulin Resistance and MicroRNA Modulators

Overview

Journal Exp Diabetes Res

Specialty Endocrinology

Date 2011 Oct 7

PMID 21977024

Citations 13

Authors

Lakshmi Pulakat

Annayya R Aroor

Rukhsana Gul

James R Sowers

Affiliations

Soon will be listed here.

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.

Citing Articles

mTOR Dysregulation, Insulin Resistance, and Hypertension.

Stanciu S, Jinga M, Miricescu D, Stefani C, Nica R, Stanescu-Spinu I Biomedicines. 2024; 12(8).

PMID: 39200267 PMC: 11351979. DOI: 10.3390/biomedicines12081802.

Comparison of Cardiac miRNA Transcriptomes Induced by Diabetes and Rapamycin Treatment and Identification of a Rapamycin-Associated Cardiac MicroRNA Signature.

Belenchia A, Gavini M, Toedebusch R, Demarco V, Pulakat L Oxid Med Cell Longev. 2019; 2018:8364608.

PMID: 30647817 PMC: 6311877. DOI: 10.1155/2018/8364608.

The two faces of miR-29.

Slusarz A, Pulakat L J Cardiovasc Med (Hagerstown). 2015; 16(7):480-90.

PMID: 25689084 PMC: 4449311. DOI: 10.2459/JCM.0000000000000246.

Noncoding RNA in age-related cardiovascular diseases.

Greco S, Gorospe M, Martelli F J Mol Cell Cardiol. 2015; 83():142-55.

PMID: 25640162 PMC: 5509469. DOI: 10.1016/j.yjmcc.2015.01.011.

Overnutrition, mTOR signaling, and cardiovascular diseases.

Jia G, Aroor A, Martinez-Lemus L, Sowers J Am J Physiol Regul Integr Comp Physiol. 2014; 307(10):R1198-206.

PMID: 25253086 PMC: 4233289. DOI: 10.1152/ajpregu.00262.2014.

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