Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "Larsen 2013 J Am Coll Cardiol"

From Bioblast
Β 
(2 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{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(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).
|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(10) may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism.
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(10) content was determined.
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(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.
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(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.
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(10), Simvastatin-treated patients, Muscle pain, [[OXPHOS]]
|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
Line 25: Line 25:
|diseases=Diabetes
|diseases=Diabetes
|couplingstates=OXPHOS
|couplingstates=OXPHOS
|substratestates=CI, CII, CI&II
|pathways=N, S, NS
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
}}
}}

Latest revision as of 15:45, 5 March 2019

Publications in the MiPMap
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.

Β» PMID: 23287371 Open Access

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