Difference between revisions of "Larsen 2013 J Am Coll Cardiol"
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{{Publication | {{Publication | ||
|title=Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F (2013) Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol 61: 44-53. | |title=Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F (2013) Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol 61:44-53. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23287371 PMID: 23287371] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23287371 PMID: 23287371 Open Access] | ||
|authors=Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F | |authors=Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F | ||
|year=2013 | |year=2013 | ||
|journal=J Am Coll Cardiol | |journal=J Am Coll Cardiol | ||
|abstract=OBJECTIVES: Glucose tolerance and skeletal muscle coenzyme Q | |abstract=OBJECTIVES: Glucose tolerance and skeletal muscle coenzyme Q<sub>10</sub> (Q<sub>10</sub>) 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 | 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<sub>10</sub> 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 | 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<sub>10</sub> content was determined. | ||
RESULTS: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q | RESULTS: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q<sub>10</sub> 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 | CONCLUSIONS: These simvastatin-treated patients were glucose intolerant. A decreased Q<sub>10</sub> 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. | ||
|keywords=Coenzyme Q | |keywords=Coenzyme Q<sub>10</sub>, Simvastatin-treated patients, Muscle pain, [[OXPHOS]], Glucose intolerance; Mitochondrial function; Q<sub>10</sub> protein content; Simvastatin | ||
|mipnetlab=DK Copenhagen Dela F | |mipnetlab=DK Copenhagen Dela F, DK Copenhagen Larsen S | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, mt-Biogenesis; mt-density, Pharmacology; toxicology | |area=Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology | ||
|organism=Human | |organism=Human | ||
|tissues=Skeletal muscle | |tissues=Skeletal muscle | ||
|preparations=Permeabilized tissue | |preparations=Permeabilized tissue | ||
|enzymes=Complex I, Complex II; | |enzymes=Complex I, Complex II;succinate dehydrogenase | ||
|diseases=Diabetes | |||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
| | |pathways=N, S, NS | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 15:45, 5 March 2019
Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F (2013) Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol 61:44-53. |
Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F (2013) J Am Coll Cardiol
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. β’ Keywords: Coenzyme Q10, Simvastatin-treated patients, Muscle pain, OXPHOS, Glucose intolerance; Mitochondrial function; Q10 protein content; Simvastatin
β’ O2k-Network Lab: DK Copenhagen Dela F, DK Copenhagen Larsen S
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology
Pathology: Diabetes
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase
Coupling state: OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k