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Submaximal ADP‐stimulated respiration is impaired in ZDF rats and recovered by resveratrol
Author(s) -
Smith Brennan K.,
Perry Christopher G. R.,
Herbst Eric A. F.,
Ritchie Ian R.,
Beaudoin MarieSoleil,
Smith Jeffrey C.,
Neufer P. Darrell,
Wright David C.,
Holloway Graham P.
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.259226
Subject(s) - medicine , skeletal muscle , endocrinology , respiration , insulin resistance , mitochondrion , resveratrol , reactive oxygen species , mitochondrial ros , chemistry , cellular respiration , biology , diabetes mellitus , biochemistry , anatomy
Key points• Disparity exists within the literature surrounding mitochondrial dysfunction and insulin resistance and previous reports have primarily examined mitochondrial function as a capacity measurement. • We show that submaximal ADP‐stimulated respiration rates are lower in ZDF rats, which coincides with decreased adenine nucleotide translocase 2 (ANT2) protein content. • Supplementation of ZDF rats with resveratrol improves skeletal muscle insulin sensitivity, increases submaximal ADP‐stimulated respiration rates and increases ANT2 protein content. • Improvements in the ability of ADP to attenuate mitochondrial reactive oxygen species (ROS) emission and cellular redox balance were also observed following resveratrol supplementation. • These data suggest that mitochondrial dysfunction is present in skeletal muscle insulin resistance when assessed at submaximal ADP concentrations and that ADP dynamics may influence skeletal muscle insulin sensitivity through alterations in the propensity for ROS formation.Abstract Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the aetiology of skeletal muscle insulin resistance, although there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturating ADP, but ATP turnover and the resultant ADP is thought to limit respiration in vivo . Therefore, we investigated the potential link between submaximal ADP‐stimulated respiration rates, ROS generation and skeletal muscle insulin sensitivity in a model of type 2 diabetes mellitus, the ZDF rat. Utilizing permeabilized muscle fibres we observed that submaximal ADP‐stimulated respiration rates (250–2000 μ m ADP) were lower in ZDF rats than in lean controls, which coincided with decreased adenine nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP‐stimulated respiration occurred in the absence of a decrease in electron transport chain function. Treating ZDF rats with resveratrol improved skeletal muscle insulin resistance and this was associated with elevated submaximal ADP‐stimulated respiration rates as well as an increase in ANT2 protein content. These results coincided with a greater ability of ADP to attenuate mitochondrial ROS emission and an improvement in cellular redox balance. Together, these data suggest that mitochondrial dysfunction is present in skeletal muscle insulin resistance when assessed at submaximal ADP concentrations and that ADP dynamics may influence skeletal muscle insulin sensitivity through alterations in the propensity for mitochondrial ROS emission.