Boushel 2007 Diabetologia
| Boushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Patients with Type 2 Diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50: 790-796. |
Boushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Diabetologia
Abstract: Aims/hypothesis: Insulin resistance and type 2 diabetes are associated with mitochondrial dysfunction. The aim of the present study was to test the hypothesis that oxidative phosphorylation and electron transport capacity are diminished in the skeletal muscle of type 2 diabetic subjects, as a result of a reduction in the mitochondrial content. Materials and methods: The O2 flux capacity of permeabilised muscle fibres from biopsies of the quadriceps in healthy subjects (n=8; age 58±2 years [mean±SEM]; BMI 28±1 kg/m2; fasting plasma glucose 5.4±0.2 mmol/l) and patients with type 2 diabetes (n=11; age 62±2 years; BMI 32±2 kg/m2; fasting plasma glucose 9.0±0.8 mmol/l) was measured by high-resolution respirometry.
Results: O2 flux expressed per mg of muscle (fresh weight) during ADP-stimulated state 3 respiration was lower ( p<0.05) in patients with type 2 diabetes in the presence of complex I substrate (glutamate) (31±2 vs 43±3 pmol O2 s-1 mg-1) and in response to glutamate + succinate (parallel electron input from complexes I and II) (63±3 vs 85±6 pmol s-1 mg-1). Further increases in O2 flux capacity were observed in response to uncoupling by FCCP, but were again lower ( p<0.05) in type 2 diabetic patients than in healthy control subjects (86±4 vs 109±8 pmol s-1 mg-1). However, when O2 flux was normalised for mitochondrial DNA content or citrate synthase activity,there were no differences in oxidative phosphorylation or electron transport capacity between patients with type 2 diabetes and healthy control subjects.
Conclusions/interpretation: Mitochondrial function is normal in type 2 diabetes. Blunting of coupled and uncoupled respiration in type 2 diabetic patients can be attributed to lower mitochondrial content. • Keywords: Diabetes, Mitochondria, Skeletal muscle
• O2k-Network Lab: DK_Copenhagen_Dela F, AT_Innsbruck_Gnaiger E, DK_Copenhagen_Boushel RC, AT Innsbruck MitoCom
Labels:
Pathology: Diabetes
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Organism: Human
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Regulation: Mitochondrial Biogenesis; Mitochondrial Density"Mitochondrial Biogenesis; Mitochondrial Density" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Substrate; Glucose; TCA Cycle"Substrate; Glucose; TCA Cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
Corrections
Some concentrations of substrates applied in the respirometric protocols are higher than in MiPNet09.12, but have actually been applied according to MiPNet09.12.
