| Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. | |
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MedLine Citation:
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PMID: 23287371 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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OBJECTIVES: Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9). BACKGROUND: A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q(10) may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism. METHODS: Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q(10) content was determined. RESULTS: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q(10) content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I- and complex II-linked substrates were used alone, but when complex I + II-linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects. CONCLUSIONS: These simvastatin-treated patients were glucose intolerant. A decreased Q(10) content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment. |
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Authors:
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Steen Larsen; Nis Stride; Martin Hey-Mogensen; Christina N Hansen; Lia E Bang; Henning Bundgaard; Lars B Nielsen; Jørn W Helge; Flemming Dela |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of the American College of Cardiology Volume: 61 ISSN: 1558-3597 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
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Languages: eng Pagination: 44-53 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: stelar@sund.ku.dk. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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