Smith 2013 J Physiol

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Smith BK, Perry CG, Herbst EA, Ritchie IR, Beaudoin MS, Smith JC, Neufer PD, Wright DC, Holloway GP (2013) Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol. J Physiol 591:6089-101.

» PMID: 24081154 Open Access

Smith BK, Perry CG, Herbst EA, Ritchie IR, Beaudoin MS, Smith JC, Neufer PD, Wright DC, Holloway GP (2013) J Physiol

Abstract: Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the etiology of skeletal muscle insulin resistance, however there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturating ADP, however 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 T2DM, the ZDF rat. Utilizing permeabilized muscle fibres we observed that submaximal ADP-stimulated respiration rates (250-2000 μM ADP) were lower in ZDF rats compared to 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. Altogether, 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.

Keywords: Diabetes mellitus, Mitochondria, Skeletal muscle

O2k-Network Lab: CA Guelph Holloway GP, CA Toronto Perry CG, US NC Greenville Neufer PD


Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology  Pathology: Diabetes 

Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Adenine nucleotide translocase 

Coupling state: LEAK  Pathway: N, NS  HRR: Oxygraph-2k 

Resveratrol