Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol.
Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol.
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ZDF 大鼠中 ADP 刺激的次最大呼吸受到损害，但可通过白藜芦醇恢复。
DOI：
10.1113/jphysiol.2013.259226
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Holloway,GrahamP
中科院分区：
文献类型：
--
作者：
Smith,BrennanK;Perry,ChristopherGR;Herbst,EricAF;Ritchie,IanR;Beaudoin,Marie-Soleil;Smith,JeffreyC;Neufer,PDarrell;Wright,DavidC;Holloway,GrahamP
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.AbstractMitochondrial 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 respirationin 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 μmADP) 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.
