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Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance in...

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Autores principales: Abu Bakar, Mohamad Hafizi, Cheng, Kian-Kai, Sarmidi, Mohamad Roji, Yaakob, Harisun, Zaman Huri, Hasniza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272652/
https://www.ncbi.nlm.nih.gov/pubmed/25961164
http://dx.doi.org/10.3390/molecules20058242
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author Abu Bakar, Mohamad Hafizi
Cheng, Kian-Kai
Sarmidi, Mohamad Roji
Yaakob, Harisun
Zaman Huri, Hasniza
author_facet Abu Bakar, Mohamad Hafizi
Cheng, Kian-Kai
Sarmidi, Mohamad Roji
Yaakob, Harisun
Zaman Huri, Hasniza
author_sort Abu Bakar, Mohamad Hafizi
collection PubMed
description Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
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spelling pubmed-62726522019-01-07 Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells Abu Bakar, Mohamad Hafizi Cheng, Kian-Kai Sarmidi, Mohamad Roji Yaakob, Harisun Zaman Huri, Hasniza Molecules Article Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells. MDPI 2015-05-07 /pmc/articles/PMC6272652/ /pubmed/25961164 http://dx.doi.org/10.3390/molecules20058242 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abu Bakar, Mohamad Hafizi
Cheng, Kian-Kai
Sarmidi, Mohamad Roji
Yaakob, Harisun
Zaman Huri, Hasniza
Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title_full Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title_fullStr Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title_full_unstemmed Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title_short Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
title_sort celastrol protects against antimycin a-induced insulin resistance in human skeletal muscle cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272652/
https://www.ncbi.nlm.nih.gov/pubmed/25961164
http://dx.doi.org/10.3390/molecules20058242
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