Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes

R Rabøl; R Boushel; T Almdal; C.N. Hansen; T Ploug; Steen Bendix Haugaard; C Prats; S Madsbad; F Dela; R Rabøl; R Boushel; T Almdal; C N Hansen; T Ploug; S B Haugaard; C Prats; S Madsbad; F Dela

doi:10.1111/j.1463-1326.2010.01237.x

Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes

R Rabøl, R Boushel, T Almdal, C.N. Hansen, T Ploug, Steen Bendix Haugaard, C Prats, S Madsbad, F Dela, R Rabøl, R Boushel, T Almdal, C N Hansen, T Ploug, S B Haugaard, C Prats, S Madsbad, F Dela

27 Citations (Scopus)

Abstract

Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM).Methods: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [n = 12; age, 59.2 ± 2.2 years; body mass index (BMI), 29.6 ± 0.7 kg/m²] or PIO (30 mg once daily) (n = 9; age, 56.3 ± 2.4 years; BMI, 29.5 ± 1.5 kg/m²). An age- and BMI-matched control group was also included (n = 8; age, 61.8 ± 2.3 years; BMI, 28.4 ± 0.6 kg/m²). Insulin sensitivity, citrate synthase- and β-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I-IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry.Results: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I-IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged.Conclusions: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects.

Original language	English
Journal	Diabetic Medicine
Volume	12
Issue number	9
Pages (from-to)	806-14
Number of pages	8
ISSN	0742-3071
DOIs	https://doi.org/10.1111/j.1463-1326.2010.01237.x
Publication status	Published - Sept 2010

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10.1111/j.1463-1326.2010.01237.x

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Rabøl, R., Boushel, R., Almdal, T., Hansen, C. N., Ploug, T., Haugaard, S. B., Prats, C., Madsbad, S., Dela, F., Rabøl, R., Boushel, R., Almdal, T., Hansen, C. N., Ploug, T., Haugaard, S. B., Prats, C., Madsbad, S., & Dela, F. (2010). Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes. Diabetic Medicine, 12(9), 806-14. https://doi.org/10.1111/j.1463-1326.2010.01237.x

Rabøl, R, Boushel, R, Almdal, T, Hansen, CN, Ploug, T , Haugaard, SB , Prats, C , Madsbad, S , Dela, F, Rabøl, R, Boushel, R, Almdal, T, Hansen, CN, Ploug, T, Haugaard, SB, Prats, C, Madsbad, S & Dela, F 2010, 'Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes', Diabetic Medicine, vol. 12, no. 9, pp. 806-14. https://doi.org/10.1111/j.1463-1326.2010.01237.x

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title = "Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes",

abstract = "Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM).Methods: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [n = 12; age, 59.2 ± 2.2 years; body mass index (BMI), 29.6 ± 0.7 kg/m2] or PIO (30 mg once daily) (n = 9; age, 56.3 ± 2.4 years; BMI, 29.5 ± 1.5 kg/m2). An age- and BMI-matched control group was also included (n = 8; age, 61.8 ± 2.3 years; BMI, 28.4 ± 0.6 kg/m2). Insulin sensitivity, citrate synthase- and β-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I-IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry.Results: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I-IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged.Conclusions: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects.",

author = "R Rab{\o}l and R Boushel and T Almdal and C.N. Hansen and T Ploug and Haugaard, {Steen Bendix} and C Prats and S Madsbad and F Dela and R Rab{\o}l and R Boushel and T Almdal and Hansen, {C N} and T Ploug and Haugaard, {S B} and C Prats and S Madsbad and F Dela",

year = "2010",

month = sep,

doi = "10.1111/j.1463-1326.2010.01237.x",

language = "English",

volume = "12",

pages = "806--14",

journal = "Diabetic Medicine",

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TY - JOUR

T1 - Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes

AU - Rabøl, R

AU - Boushel, R

AU - Almdal, T

AU - Hansen, C.N.

AU - Ploug, T

AU - Haugaard, Steen Bendix

AU - Prats, C

AU - Madsbad, S

AU - Dela, F

AU - Rabøl, R

AU - Boushel, R

AU - Almdal, T

AU - Hansen, C N

AU - Ploug, T

AU - Haugaard, S B

AU - Prats, C

AU - Madsbad, S

AU - Dela, F

PY - 2010/9

Y1 - 2010/9

N2 - Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM).Methods: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [n = 12; age, 59.2 ± 2.2 years; body mass index (BMI), 29.6 ± 0.7 kg/m2] or PIO (30 mg once daily) (n = 9; age, 56.3 ± 2.4 years; BMI, 29.5 ± 1.5 kg/m2). An age- and BMI-matched control group was also included (n = 8; age, 61.8 ± 2.3 years; BMI, 28.4 ± 0.6 kg/m2). Insulin sensitivity, citrate synthase- and β-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I-IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry.Results: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I-IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged.Conclusions: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects.

AB - Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM).Methods: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [n = 12; age, 59.2 ± 2.2 years; body mass index (BMI), 29.6 ± 0.7 kg/m2] or PIO (30 mg once daily) (n = 9; age, 56.3 ± 2.4 years; BMI, 29.5 ± 1.5 kg/m2). An age- and BMI-matched control group was also included (n = 8; age, 61.8 ± 2.3 years; BMI, 28.4 ± 0.6 kg/m2). Insulin sensitivity, citrate synthase- and β-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I-IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry.Results: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I-IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged.Conclusions: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects.

U2 - 10.1111/j.1463-1326.2010.01237.x

DO - 10.1111/j.1463-1326.2010.01237.x

M3 - Journal article

C2 - 20649633

SN - 0742-3071

VL - 12

SP - 806

EP - 814

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 9

ER -

Opposite effects of pioglitazone and rosiglitazone on mitochondrial respiration in skeletal muscle of patients with type 2 diabetes

Abstract

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