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Simvastatin Effects on Skeletal Muscle: Relation to Decreased Mitochondrial Function and Glucose Intolerance
- Source :
-
Journal of the American College of Cardiology (JACC) . Jan2013, Vol. 61 Issue 1, p44-53. 10p. - Publication Year :
- 2013
-
Abstract
- Objectives: Glucose tolerance and skeletal muscle coenzyme Q10 (Q10) 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 Q10 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 Q10 content was determined. Results: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q10 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 Q10 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 07351097
- Volume :
- 61
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of the American College of Cardiology (JACC)
- Publication Type :
- Academic Journal
- Accession number :
- 84645574
- Full Text :
- https://doi.org/10.1016/j.jacc.2012.09.036