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Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448087/ https://www.ncbi.nlm.nih.gov/pubmed/23016132 http://dx.doi.org/10.3390/nu4081058 |
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author | Nguyen, Van Anh Le, Tran Tong, Ming Silbermann, Elizabeth Gundogan, Fusun de la Monte, Suzanne M. |
author_facet | Nguyen, Van Anh Le, Tran Tong, Ming Silbermann, Elizabeth Gundogan, Fusun de la Monte, Suzanne M. |
author_sort | Nguyen, Van Anh |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3448087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-34480872012-09-26 Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy Nguyen, Van Anh Le, Tran Tong, Ming Silbermann, Elizabeth Gundogan, Fusun de la Monte, Suzanne M. Nutrients Article 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. MDPI 2012-08-20 /pmc/articles/PMC3448087/ /pubmed/23016132 http://dx.doi.org/10.3390/nu4081058 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Nguyen, Van Anh Le, Tran Tong, Ming Silbermann, Elizabeth Gundogan, Fusun de la Monte, Suzanne M. Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title | Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title_full | Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title_fullStr | Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title_full_unstemmed | Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title_short | Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy |
title_sort | impaired insulin/igf signaling in experimental alcohol-related myopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448087/ https://www.ncbi.nlm.nih.gov/pubmed/23016132 http://dx.doi.org/10.3390/nu4081058 |
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