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.

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Abstract

Objective - Mitochondrial dysfunction and fat accumulation in skeletal muscle (IMCL) has been linked to development of type 2 diabetes. We examined if exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes (T2D). Methods - 18 male T2D and 20 healthy male control subjects (C) of comparable body weight, BMI, age and VO2max, performed a 12 week combined progressive training program (3x/week, 45 minutes/session). In vivo mitochondrial function (MRS), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry) and IMCL content (histochemically) were measured before and after training. Results - Mitochondrial function was lower in T2D compared to C (p=0.03), improved by training in C (+28%, p=0.02) and restored to control values in T2D (+48%, p<0.01). Insulin sensitivity tended to improve in C (delta Rd +8%, p=0.08) and improved significantly in T2D (delta Rd +63%, p<0.01). Suppression of insulin stimulated endogenous glucose production improved in both groups (EGP -64%, p<0.01 in C and -52%, p<0.01 in T2D). After training, metabolic flexibility in T2D was restored (delta RER +63%, p=0.01), but was unchanged in C (delta RER +7%, p=0.22). Starting with comparable pre-training IMCL levels, training tended to increase IMCL content in T2D (+27%, p=0.10), especially in type 2 muscle fibers. Conclusion - Exercise training restored in vivo mitochondrial function in T2D. Insulin mediated glucose disposal and metabolic flexibility improved in T2D 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.
Original languageEnglish
Pages (from-to)572-579
Number of pages8
JournalDiabetes
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • INTRAMYOCELLULAR LIPID-CONTENT
  • HUMAN SKELETAL-MUSCLE
  • MAGNETIC-RESONANCE-SPECTROSCOPY
  • UNCOUPLING PROTEIN-3 CONTENT
  • OXIDATIVE CAPACITY
  • ROSIGLITAZONE TREATMENT
  • TRIGLYCERIDE SYNTHESIS
  • SUBSTRATE OXIDATION
  • GLUCOSE DISPOSAL
  • ENZYME-ACTIVITY

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