title: Hydrogen peroxide production is not primarily increased in human myotubes established from type 2 diabetic subjects.
abstract: BACKGROUND
  Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes is primarily increased or a secondary adaptation to environmental, lifestyle, and hormonal factors.
  
  
  OBJECTIVE
  This study investigates whether ROS production is primarily increased in isolated diabetic myotubes.
  
  
  METHODS
  Mitochondrial membrane potential, hydrogen peroxide (H(2)O(2)), superoxide, and mitochondrial mass were determined in human myotubes precultured under normophysiological conditions. Furthermore, the corresponding ATP synthesis was measured in isolated mitochondria.
  
  
  METHODS
  Muscle biopsies were taken from 10 lean subjects, 10 obese subjects, and 10 subjects with type 2 diabetes; satellite cells were isolated, cultured, and differentiated to myotubes.
  
  
  RESULTS
  Mitochondrial mass, membrane potential/mitochondrial mass, and superoxide-production/mitochondrial mass were not different between groups. In contrast, H(2)O(2) production/mitochondrial mass and ATP production were significantly reduced in diabetic myotubes compared to lean controls (P < 0.05). The ATP/H(2)O(2) ratios were not significantly different between groups.
  
  
  CONCLUSIONS
  Our result indicates that the ROS production is not primarily increased in diabetic myotubes but rather is reduced. Moreover, the comparable ATP/H(2)O(2) ratios indicate that the reduced ROS production in diabetic myotubes parallels the reduced ATP production because ROS production in diabetic myotubes must be considered to be in a proportion comparable to lean. Thus, the increased ROS production seen in skeletal muscle of type 2 diabetic patients is an adaptation to the in vivo conditions.
authors: Department of Pathology, Laboratory for Molecular Physiology, and Department of Endocrinology, Odense University Hospital, DK-5000 Odense, Denmark.
authors: A D
authors: AD
authors: Minet
authors: M
authors: M
authors: Gaster
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide