Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals

Abstract

Aims/hypothesis: We previously showed that type 2 diabetic patients are characterised by compromised intrinsic mitochondrial function. Here, we examined if exercise training could increase intrinsic mitochondrial function in diabetic patients compared with control individuals.

Methods: Fifteen male type 2 diabetic patients and 14 male control individuals matched for age, BMI and VO(2max) enrolled in a 12 week exercise intervention programme. Ex vivo mitochondrial function was assessed by high-resolution respirometry in permeabilised muscle fibres from vastus lateralis muscle. Before and after training, insulin-stimulated glucose disposal was examined during a hyperinsulinaemic-euglycaemic clamp.

Results: Diabetic patients had intrinsically lower ADP-stimulated state 3 respiration and lower carbonyl cyanide 4-(trifluoro-methoxy)phenylhydrazone (FCCP)-induced maximal oxidative respiration, both on glutamate and on glutamate and succinate, and in the presence of palmitoyl-carnitine (p < 0.05). After training, diabetic patients and control individuals showed increased state 3 respiration on the previously mentioned substrates (p < 0.05); however, an increase in FCCP-induced maximal oxidative respiration was observed only in diabetic patients (p < 0.05). The increase in mitochondrial respiration was accompanied by a 30% increase in mitochondrial content upon training (p < 0.01). After adjustment for mitochondrial density, state 3 and FCCP-induced maximal oxidative respiration were similar between groups after training. Improvements in mitochondrial respiration were paralleled by improvements in insulin-stimulated glucose disposal in diabetic patients, with a tendency for this in control individuals.

Conclusions/interpretation: We confirmed lower intrinsic mitochondrial function in diabetic patients compared with control individuals. Diabetic patients increased their mitochondrial content to the same extent as control individuals and had similar intrinsic mitochondrial function, which occurred parallel with improved insulin sensitivity.

Figures

Fig. 1

Intrinsic mitochondrial respiration ([pmol mg−1 s−1]/[mtDNA copy number × 106]) in 17 control individuals (white bars) vs 15 diabetic patients (black bars) before training. a In glutamate and succinate. Means ± SE. *p < 0.05; †p = 0.09. b In glutamate and succinate with the addition of palmitoyl-carnitine. Means ± SE. *p < 0.05; †p = 0.06. M, malate alone; MP, malate with palmitoyl-carnitine

Fig. 2

Intrinsic mitochondrial respiration ([pmol mg−1 s−1]/[mtDNA copy number × 106]) for 14 control individuals and 15 diabetic patients before training and control individuals after training. a In glutamate and succinate. White and light-grey bars represent control individuals before and after training, respectively; black and dark-grey bars represent diabetic patients before and after training, respectively. Means ± SE. *p < 0.05. b In glutamate and succinate with the addition of palmitoyl-carnitine. Means ± SE. *p < 0.05. M, malate alone; MP, malate with palmitoyl-carnitine