Reactive oxygen species enhance mitochondrial function, insulin sensitivity and glucose uptake in skeletal muscle of senescence accelerated prone mice SAMP8

Whereas reactive oxygen species (ROS) can have opposite impacts on insulin signaling, they have mainlybeen associated with mitochondrial dysfunction in skeletal muscle. We analyzed the relationship betweenthese three features in skeletal muscle of senescence accelerated mice (SAM) prone (P8), which arecharacterized by enhanced oxidative stress compared to SAM resistant (R1). Oxidative stress, ROSproduction, antioxidant system, mitochondrial content and functioning, as well as in vitro and in vivo insulinsignaling were investigated in gastrocnemius and quadriceps muscles. In SAMP8 compared to SAMR1,muscle content in carbonylated proteins was two-fold (p<0.01) and ROS production by xanthine oxidase70% (p<0.05) higher. Furthermore, insulin-induced Akt phosphorylation measured in vivo and ex vivo aswell as muscle glucose uptake measured ex vivo were significantly higher (p<0.05). Mitochondrialrespiration evidenced uncoupling and higher respiration rates with substrates of complexes II and IV, inagreement with higher maximal activity of complexes II and IV (+18 and 62%, respectively, p<0.05). Bycontrast, maximal activity of complex I was 22% lower (p