AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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 diabeticparticipants. METHODS: Ten lean healthy, ten obese non-diabetic and ten type 2 diabeticparticipants 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 diabeticparticipants 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-diabeticparticipants, 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 diabetesparticipants. CONCLUSIONS/ INTERPRETATION: Since, in absolute terms, the maximal capacity for mitochondrial ROS production was not increased in either obese insulin-resistant participants or in type 2 diabeticparticipants, 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: S Jacob; P Ruus; R Hermann; H J Tritschler; E Maerker; W Renn; H J Augustin; G J Dietze; K Rett Journal: Free Radic Biol Med Date: 1999-08 Impact factor: 7.376
Authors: Muhammad A Abdul-Ghani; Florian L Muller; Yuhong Liu; Alberto O Chavez; Bogdan Balas; Pengou Zuo; Zhi Chang; Devjit Tripathy; Rucha Jani; Marjorie Molina-Carrion; Adriana Monroy; Franco Folli; Holly Van Remmen; Ralph A DeFronzo Journal: Am J Physiol Endocrinol Metab Date: 2008-07-01 Impact factor: 4.310
Authors: S Jacob; E J Henriksen; A L Schiemann; I Simon; D E Clancy; H J Tritschler; W I Jung; H J Augustin; G J Dietze Journal: Arzneimittelforschung Date: 1995-08
Authors: Florian L Muller; Yuhong Liu; Muhammad A Abdul-Ghani; Michael S Lustgarten; Arunabh Bhattacharya; Youngmok C Jang; Holly Van Remmen Journal: Biochem J Date: 2008-01-15 Impact factor: 3.857
Authors: Vera B Schrauwen-Hinderling; Michael Roden; M Eline Kooi; Matthijs Kc Hesselink; Patrick Schrauwen Journal: Curr Opin Clin Nutr Metab Care Date: 2007-11 Impact factor: 4.294
Authors: S Larsen; N Stride; M Hey-Mogensen; C N Hansen; J L Andersen; S Madsbad; D Worm; J W Helge; F Dela Journal: Diabetologia Date: 2011-03-18 Impact factor: 10.122
Authors: M Hey-Mogensen; K Højlund; B F Vind; L Wang; F Dela; H Beck-Nielsen; M Fernström; K Sahlin Journal: Diabetologia Date: 2010-06-06 Impact factor: 10.122
Authors: Scott P Naples; Sarah J Borengasser; R Scott Rector; Grace M Uptergrove; E Matthew Morris; Catherine R Mikus; Lauren G Koch; Steve L Britton; Jamal A Ibdah; John P Thyfault Journal: Appl Physiol Nutr Metab Date: 2010-04 Impact factor: 2.665