title: Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells.
abstract: 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.
authors.affiliation: Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia. mhafizi55@live.utm.my.
authors.forename: Mohamad Hafizi
authors.initials: MH
authors.lastname: Abu Bakar
authors.affiliation: Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia. chengkiankai@cheme.utm.my.|Innovation Centre in Agritechnology for Advanced Bioprocessing (ICA), Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia. chengkiankai@cheme.utm.my.
authors.forename: Kian-Kai
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: Innovation Centre in Agritechnology for Advanced Bioprocessing (ICA), Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia. mroji@ibd.utm.my.|Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia. mroji@ibd.utm.my.
authors.forename: Mohamad Roji
authors.initials: MR
authors.lastname: Sarmidi
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia. harisun@ibd.utm.my.
authors.forename: Harisun
authors.initials: H
authors.lastname: Yaakob
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. hasnizazh@ummc.edu.my.|Clinical Investigation Centre, 13th Floor Main Tower, University Malaya Medical Centre, 59100 Lembah Pantai, Kuala Lumpur, Malaysia. hasnizazh@ummc.edu.my.
authors.forename: Hasniza Zaman
authors.initials: HZ
authors.lastname: Huri
mesh_terms: D000968:Antimycin A / Q000494:pharmacology*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000968:Antimycin A; D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases; D020011:Protective Agents; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; C050414:celastrol