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

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, Christina Neigaard

AU - Ploug, Thorkil

AU - Haugaard, S B

AU - Prats Gavalda, Clara

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.

KW - Body Mass Index

KW - Cell Respiration

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Hypoglycemic Agents

KW - Immunohistochemistry

KW - Insulin Resistance

KW - Male

KW - Middle Aged

KW - Mitochondria, Muscle

KW - Muscle, Skeletal

KW - Thiazolidinediones

U2 - 10.1111/j.1463-1326.2010.01237.x

DO - 10.1111/j.1463-1326.2010.01237.x

M3 - Journal article

C2 - 20649633

SN - 1462-8902

VL - 12

SP - 806

EP - 814

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 9

ER -