RESEARCH ARTICLE Enhanced Mitochondrial Superoxide Scavenging Does Not Improve Muscle Insulin Action in the High Fat-Fed Mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of in-sulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of su-peroxide dismutase (sod2tgmice) and/or transgenically expressing catalase within the mitochondrial matrix (mcattgmice) have increased scavenging of O2_ ˉ and H2O2, respec-tively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fedmcattg mice. The goal of the current study was to test the hypothesis that increased O2_ ˉ scaveng-ing alone or in combination with increased H2O2 scavenging (mtAOmice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unre-strained and unstressed wild type (WT), sod2tg,mcattg andmtAOmice using hyperinsuline-mic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60 % calories from fat) feeding. Glucose infu-sion rates, whole body glucose disappearance, and muscle glucose uptake during the insu-lin clamp were similar in chow- and HF-fed WT and sod2tgmice. Consistent with our previous work, HF-fedmcattgmice had improved muscle insulin action, however, an addi