Document Detail


Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance.
MedLine Citation:
PMID:  23287371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2013-01-04     Completed Date:  2013-03-12     Revised Date:  2013-09-05    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44-53     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. stelar@sund.ku.dk
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MeSH Terms
Descriptor/Qualifier:
Blood Glucose / analysis
Case-Control Studies
Cell Respiration / physiology
Electron Transport
Electron Transport Complex I / metabolism
Electron Transport Complex II / metabolism
Glucose Intolerance / etiology*
Glucose Tolerance Test
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
Insulin Resistance
Male
Middle Aged
Mitochondria, Muscle / metabolism*
Muscle Fibers, Skeletal / metabolism*
Muscle, Skeletal / metabolism
Oxidative Phosphorylation
Simvastatin / adverse effects*
Ubiquinone / analogs & derivatives*,  metabolism
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 1339-63-5/Ubiquinone; 303-98-0/coenzyme Q10; 79902-63-9/Simvastatin; EC 1.3.5.1/Electron Transport Complex II; EC 1.6.5.3/Electron Transport Complex I
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2013 Jun 11;61(23):2392-3   [PMID:  23524218 ]
J Am Coll Cardiol. 2013 Jul 16;62(3):257   [PMID:  23603699 ]
J Am Coll Cardiol. 2013 Jun 11;61(23):2393   [PMID:  23524207 ]
J Am Coll Cardiol. 2013 Jul 16;62(3):257-8   [PMID:  23603698 ]

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