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Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression.

Mallinson JE, Marimuthu K, Murton A, Selby A, Smith K, Constantin-Teodosiu D, Rennie MJ, Greenhaff PL - J. Physiol. (Lond.) (2015)

Bottom Line: Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity.Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR.Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham, NG7 2UH, UK.

No MeSH data available.


Related in: MedlinePlus

Study protocolPrimed constant infusions of stable isotope-labelled AAs ([2H5]phenylalanine and [1,2-13C] leucine) were administered for a total period of 240 min. Serum insulin was maintained at fasting concentrations (≈5 mU l−1) for 120 min and endogenous insulin production was suppressed by infusion of octreotide, and post-absorptive glucagon concentration was maintained by infusion of glucagon. After 120 min, serum insulin was raised equivalent to a fed state (≈40 mU l−1). Quadriceps muscle biopsies were taken at baseline, 120 min and 240 min.
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fig01: Study protocolPrimed constant infusions of stable isotope-labelled AAs ([2H5]phenylalanine and [1,2-13C] leucine) were administered for a total period of 240 min. Serum insulin was maintained at fasting concentrations (≈5 mU l−1) for 120 min and endogenous insulin production was suppressed by infusion of octreotide, and post-absorptive glucagon concentration was maintained by infusion of glucagon. After 120 min, serum insulin was raised equivalent to a fed state (≈40 mU l−1). Quadriceps muscle biopsies were taken at baseline, 120 min and 240 min.

Mentions: The protocol (Fig.1) was designed to allow the measurement of muscle protein synthesis (by incorporation of [1,2-13C]leucine into quadriceps muscle protein) and leg protein breakdown (as the rate of dilution of [2H5]phenylalanine) in the fasted (target serum insulin concentration of 5 mU l−1) and fed state (target serum insulin concentration of 40 mU l−1 and a constant infusion of mixed amino acids (AAs) at 10 g h−1) (Rennie et al. 1982). All subjects were asked to abstain from alcohol and exercise for 48 h prior to the experimental visit and to arrive in the morning in a fasted state. Subjects rested semi-supine before a femoral vein cannula (ES-04150; Arrow Deutschland, Neu-Isenburg, Germany) was inserted for leg venous blood sampling. A venous cannula was retrogradely inserted into a superficial vein on the dorsal surface of the non-dominant hand which was kept in a hand-warming unit (air temperature: 50–55°C) to arterialise the venous drainage of the hand (Gallen & Macdonald, 1990). Cannulas were also sited at the antecubital fossa in both forearms for infusion of mixed AAs as well as octreotide, glucagon, glucose and insulin to clamp insulin concentrations at various values. Patency of the lines was maintained using 0.9% NaCl infusions (Baxter Healthcare, Newbury, UK).


Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression.

Mallinson JE, Marimuthu K, Murton A, Selby A, Smith K, Constantin-Teodosiu D, Rennie MJ, Greenhaff PL - J. Physiol. (Lond.) (2015)

Study protocolPrimed constant infusions of stable isotope-labelled AAs ([2H5]phenylalanine and [1,2-13C] leucine) were administered for a total period of 240 min. Serum insulin was maintained at fasting concentrations (≈5 mU l−1) for 120 min and endogenous insulin production was suppressed by infusion of octreotide, and post-absorptive glucagon concentration was maintained by infusion of glucagon. After 120 min, serum insulin was raised equivalent to a fed state (≈40 mU l−1). Quadriceps muscle biopsies were taken at baseline, 120 min and 240 min.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358682&req=5

fig01: Study protocolPrimed constant infusions of stable isotope-labelled AAs ([2H5]phenylalanine and [1,2-13C] leucine) were administered for a total period of 240 min. Serum insulin was maintained at fasting concentrations (≈5 mU l−1) for 120 min and endogenous insulin production was suppressed by infusion of octreotide, and post-absorptive glucagon concentration was maintained by infusion of glucagon. After 120 min, serum insulin was raised equivalent to a fed state (≈40 mU l−1). Quadriceps muscle biopsies were taken at baseline, 120 min and 240 min.
Mentions: The protocol (Fig.1) was designed to allow the measurement of muscle protein synthesis (by incorporation of [1,2-13C]leucine into quadriceps muscle protein) and leg protein breakdown (as the rate of dilution of [2H5]phenylalanine) in the fasted (target serum insulin concentration of 5 mU l−1) and fed state (target serum insulin concentration of 40 mU l−1 and a constant infusion of mixed amino acids (AAs) at 10 g h−1) (Rennie et al. 1982). All subjects were asked to abstain from alcohol and exercise for 48 h prior to the experimental visit and to arrive in the morning in a fasted state. Subjects rested semi-supine before a femoral vein cannula (ES-04150; Arrow Deutschland, Neu-Isenburg, Germany) was inserted for leg venous blood sampling. A venous cannula was retrogradely inserted into a superficial vein on the dorsal surface of the non-dominant hand which was kept in a hand-warming unit (air temperature: 50–55°C) to arterialise the venous drainage of the hand (Gallen & Macdonald, 1990). Cannulas were also sited at the antecubital fossa in both forearms for infusion of mixed AAs as well as octreotide, glucagon, glucose and insulin to clamp insulin concentrations at various values. Patency of the lines was maintained using 0.9% NaCl infusions (Baxter Healthcare, Newbury, UK).

Bottom Line: Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity.Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR.Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Nottingham, NG7 2UH, UK.

No MeSH data available.


Related in: MedlinePlus