Oxidative stress limits exercise‐ and insulin‐stimulated muscle glucose uptake (MGU) in conscious, chow‐fed C57BL/6J mice

Abstract

Mitochondrial oxidative stress is associated with exercise‐induced muscular fatigue and insulin resistance. Catalase is an antioxidant enzyme catalyzing the breakdown of H2O2 into H2O and O2. We hypothesized that reducing oxidative stress by mitochondrial catalase overexpression would improve exercise‐ and insulin‐stimulated MGU. Muscle‐specific mitochondrial‐targeted catalase overexpressing mice (mCAT) and WT littermates were chow fed and studied at 16 wks of age. Arterial and venous catheters for sampling and infusion were implanted 5‐7 d prior to study. Rg, an index of MGU, was determined using 2‐deoxy[14C]glucose during 30 min of treadmill exercise or a 2h hyperinsulinemic‐euglycemic clamp. Fasting body weight, glucose, and insulin were the same in WT and mCAT mice. Arterial glucose and insulin were also similar in WT and mCAT mice during both exercise and the clamp. Exercise‐stimulated Rg was increased in soleus, gastrocnemius, and heart in mCAT vs WT mice. Insulin‐stimulated Rg was increased in gastrocnemius and vastus lateralis in mCAT vs WT mice. In conclusion, reduction in oxidative stress by mitochondrial catalase overexpression improved both exercise‐ and insulin‐stimulated MGU. This suggests that oxidative stress is a limitation to MGU under these conditions and mitochondrial antioxidants are potential targets for treatment of muscular fatigue as well as insulin resistance. (NIH DK54902)