title: Mitochondrial reactive oxygen species generation in obese non-diabetic and type 2 diabetic participants.
abstract: OBJECTIVE
  The aim of this study was to measure mitochondrial reactive oxygen species (ROS) production directly from skeletal muscle biopsies obtained from obese insulin-resistant non-diabetic and type 2 diabetic participants.
  
  
  METHODS
  Ten lean healthy, ten obese non-diabetic and ten type 2 diabetic participants received a euglycaemic-hyperinsulinaemic clamp to measure whole body insulin sensitivity. Mitochondria were isolated from skeletal muscle biopsies, and mitochondrial ATP synthesis and hydrogen peroxide production were measured ex vivo under conditions that maximally stimulate ATP synthesis and ROS production using chemiluminescent and fluorescent techniques, respectively.
  
  
  RESULTS
  Compared with lean controls, both obese non-diabetic and type 2 diabetic participants were resistant to insulin, and had a reduced rate of mitochondrial ATP production. Obese insulin-resistant participants had a decreased rate of mitochondrial ROS production, while ROS production rate in participants with type 2 diabetes was similar to that in lean healthy participants. In non-diabetic participants, the rate of ROS production was strongly correlated with the rate of ATP synthesis and the glucose disposal rate measured with the euglycaemic-hyperinsulinaemic clamp. The ROS/ATP ratio in obese insulin-resistant participants was similar to that in lean insulin-sensitive participants, while the ratio was significantly elevated in type 2 diabetes participants.
  
  
  CONCLUSIONS
  Since, in absolute terms, the maximal capacity for mitochondrial ROS production was not increased in either obese insulin-resistant participants or in type 2 diabetic participants, these results do not favour a role for increased mitochondrial ROS production in the pathogenesis of insulin resistance in human skeletal muscle. However, care should be taken in extrapolating these ex vivo observations to the in vivo situation.
authors.affiliation: Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive MS 7886, San Antonio, TX 78229, USA. Abdulghani@uthscsa.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Abdul-Ghani
authors.forename: R
authors.initials: R
authors.lastname: Jani
authors.forename: A
authors.initials: A
authors.lastname: Chavez
authors.forename: M
authors.initials: M
authors.lastname: Molina-Carrion
authors.forename: D
authors.initials: D
authors.lastname: Tripathy
authors.forename: R A
authors.initials: RA
authors.lastname: Defronzo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000255:Adenosine Triphosphate; D006442:Glycated Hemoglobin; D007328:Insulin; D017382:Reactive Oxygen Species