title: Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes.
abstract: OBJECTIVE
  Reduced mitochondrial capacity in skeletal muscle occurs in type 2 diabetic patients and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type 2 diabetic patients is remediable by physical activity and weight loss intervention is uncertain. We sought to address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type 2 diabetic patients and to address the relationship with amelioration of insulin resistance and hyperglycemia.
  
  
  METHODS
  Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mitochondrial DNA content, and mitochondrial enzyme activities. Glucose control, body composition, aerobic fitness, and insulin sensitivity were measured.
  
  
  RESULTS
  In response to a weight loss of 7.1 +/- 0.8% and a 12 +/- 1.6% improvement in Vo(2max) (P < 0.05), insulin sensitivity improved by 59 +/- 21% (P < 0.05). There were significant increases in skeletal muscle mitochondrial density (by 67 +/- 17%, P < 0.01), cardiolipin content (55 +/- 17%, P < 0.01), and mitochondrial oxidation enzymes. Energy expenditure during physical activity correlated with the degree of improvement in insulin sensitivity (r = 0.84, P < 0.01), and, in turn, improvement in mitochondrial content was a strong correlate of intervention-induced improvement in A1C and fasting plasma glucose.
  
  
  CONCLUSIONS
  Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type 2 diabetic patients. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions on hyperglycemia and insulin resistance.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania , USA. toledofs@upmc.edu
authors.forename: Frederico G S
authors.initials: FG
authors.lastname: Toledo
authors.forename: Elizabeta V
authors.initials: EV
authors.lastname: Menshikova
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Ritov
authors.forename: Koichiro
authors.initials: K
authors.lastname: Azuma
authors.forename: Zofia
authors.initials: Z
authors.lastname: Radikova
authors.forename: James
authors.initials: J
authors.lastname: DeLany
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
mesh_terms: D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005081:Exercise Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D007328:Insulin