title: Mitochondrial function in skeletal muscle is normal and unrelated to insulin action in young men born with low birth weight.
abstract: OBJECTIVE
  Low birth weight (LBW) is an independent risk factor of insulin resistance and type 2 diabetes. Recent studies suggest that mitochondrial dysfunction and impaired expression of genes involved in oxidative phosphorylation (OXPHOS) may play a key role in the pathogenesis of insulin resistance in aging and type 2 diabetes. The aim of this study was to determine whether LBW in humans is associated with mitochondrial dysfunction in skeletal muscle.
  
  
  METHODS
  Mitochondrial capacity for ATP synthesis was assessed by (31)phosphorus magnetic resonance spectroscopy in forearm and leg muscles in 20 young, lean men with LBW and 26 matched controls. On a separate day, a hyperinsulinemic euglycemic clamp with excision of muscle biopsies and dual-energy x-ray absorptiometry scanning was performed. Muscle gene expression of selected OXPHOS genes was determined by quantitative real-time PCR.
  
  
  RESULTS
  The LBW subjects displayed a variety of metabolic and prediabetic abnormalities, including elevated fasting blood glucose and plasma insulin levels, reduced insulin-stimulated glycolytic flux, and hepatic insulin resistance. Nevertheless, in vivo mitochondrial function was normal in LBW subjects, as was the expression of OXPHOS genes.
  
  
  CONCLUSIONS
  These data support and expand previous findings of abnormal glucose metabolism in young men with LBW. In addition, we found that the young, healthy men with LBW exhibited hepatic insulin resistance. However, the study does not support the hypothesis that muscle mitochondrial dysfunction per se is the underlying key metabolic defect that explains or precedes whole body insulin resistance in LBW subjects at risk for developing type 2 diabetes.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820 Gentofte, Denmark. chbe@steno.dk
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brøns
authors.forename: Christine B
authors.initials: CB
authors.lastname: Jensen
authors.forename: Heidi
authors.initials: H
authors.lastname: Storgaard
authors.forename: Amra
authors.initials: A
authors.lastname: Alibegovic
authors.forename: Stine
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Bjørn
authors.initials: B
authors.lastname: Quistorff
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
mesh_terms: D000328:Adult; D015444:Exercise / Q000502:physiology; D015870:Gene Expression; D015309:Glucose Clamp Technique; D006801:Humans; D007230:Infant, Low Birth Weight / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology*; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008931:Mitochondria, Muscle / Q000502:physiology*; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010085:Oxidative Phosphorylation
chemical_list: D007328:Insulin