Cardiac Insulin Resistance and MicroRNA Modulators. (29th September 2011)

• Record Type: Journal Article
• Authors: Pulakat, Lakshmi; Aroor, Annayya R.; Gul, Rukhsana; Sowers, James R.
• Other Names: Ren Jun Academic Editor.
• Is Part Of: Experimental diabetes research. Volume 2012(2012)
• Publication Date: 2011-09-29
• Subjects: Diabetes -- Research -- Periodicals; Diabetes -- Research; Periodicals; 616.462
• DOI: 10.1155/2012/654904
• Languages: English
• ISSNs: 1687-5214

Abstract

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.