Nutrients 2012, 4(8), 1058-1075; doi:10.3390/nu4081058

Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy

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Received: 3 July 2012; in revised form: 7 August 2012 / Accepted: 13 August 2012 / Published: 20 August 2012
(This article belongs to the Special Issue Alcohol and Health)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8) or 35.5% (N = 13) ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration.
Keywords: alcohol; myopathy; insulin resistance; signal transduction; experimental model; multiplex ELISA; Akt pathway; gene expression; acetylcholine; oxidative stress; mitochondrial dysfunction
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MDPI and ACS Style

Nguyen, V.A.; Le, T.; Tong, M.; Silbermann, E.; Gundogan, F.; de la Monte, S.M. Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy. Nutrients 2012, 4, 1058-1075.

AMA Style

Nguyen VA, Le T, Tong M, Silbermann E, Gundogan F, de la Monte SM. Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy. Nutrients. 2012; 4(8):1058-1075.

Chicago/Turabian Style

Nguyen, Van Anh; Le, Tran; Tong, Ming; Silbermann, Elizabeth; Gundogan, Fusun; de la Monte, Suzanne M. 2012. "Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy." Nutrients 4, no. 8: 1058-1075.

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