title: Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University Medical Centre, P.O. Box 616, NL6200 MD Maastricht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Phielix
authors.forename: R
authors.initials: R
authors.lastname: Meex
authors.forename: E
authors.initials: E
authors.lastname: Moonen-Kornips
authors.forename: M K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: P
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption
chemical_list: D001786:Blood Glucose; D007328:Insulin