title: Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.
abstract: OBJECTIVE
  Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes.
  
  
  METHODS
  Eighteen male type 2 diabetic and 20 healthy male control subjects of comparable body weight, BMI, age, and VO2max participated in a 12-week combined progressive training program (three times per week and 45 min per session). In vivo mitochondrial function (assessed via magnetic resonance spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry), and IMCL content (histochemically) were measured before and after training.
  
  
  RESULTS
  Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P < 0.01). Insulin sensitivity tended to improve in control subjects (delta Rd 8% increase; P = 0.08) and improved significantly in type 2 diabetic subjects (delta Rd 63% increase; P < 0.01). Suppression of insulin-stimulated endogenous glucose production improved in both groups (-64%; P < 0.01 in control subjects and -52% in diabetic subjects; P < 0.01). After training, metabolic flexibility in type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with comparable pretraining IMCL levels, training tended to increase IMCL content in type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle fibers.
  
  
  CONCLUSIONS
  Exercise training restored in vivo mitochondrial function in type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic flexibility improved in type 2 diabetic subjects in the face of near-significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity.
authors.affiliation: Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Ruth C R
authors.initials: RC
authors.lastname: Meex
authors.forename: Vera B
authors.initials: VB
authors.lastname: Schrauwen-Hinderling
authors.forename: Esther
authors.initials: E
authors.lastname: Moonen-Kornips
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Marco
authors.initials: M
authors.lastname: Mensink
authors.forename: Esther
authors.initials: E
authors.lastname: Phielix
authors.forename: Tineke
authors.initials: T
authors.lastname: van de Weijer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Sels
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D005081:Exercise Therapy / Q000379:methods*; D005223:Fats / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D010759:Phosphorus Isotopes
chemical_list: D001786:Blood Glucose; D005223:Fats; D010759:Phosphorus Isotopes