Dexamethasone negative side effects on insulin signaling is prevented by Exercise Training: role of IRS‐1 and p‐AKT

Abstract

Dexamethasone (Dexa) is widely used as treatment of chronic inflammatory diseases, however high doses of glucocorticoids cause reduction in skeletal muscle insulin‐dependent glucose uptake. Exercise training (T) causes opposite effects. This study investigated whether physical exercise could prevent the side effects of Dexa in the skeletal muscle insulin‐dependent glucose uptake. Rats underwent a training period where they were either submitted to a running protocol (8 weeks) or kept sedentary. After this T period, the animals underwent Dexa treatment (1 mg/kg/day, i.p., 10 days) concomitant with T. An ipGTT was performed and the area under the glucose curve (AUC) was calculated. Western blot analysis was performed to identify IRS‐1 and p‐AKT protein expression in the tibialis anterior (TA) muscle. The AUC was 39% higher for Dexa‐treated rats, which was attenuated by T. Dexa significantly reduced IRS‐1 (−58%) and p‐AKT (−48%) protein expression in the TA muscle. On the other hand, T increased protein expression of IRS‐1 (112%) and p‐AKT (93%). T completely blocked the reduction of IRS‐1, and also inhibited the p‐AKT protein expression reductions in the trained group. Therefore, T prevented the Dexa‐reductions of IRS‐1 and p‐AKT protein expression in the skeletal muscle and may be a good strategy to prevent Dexa‐induced peripheral insulin resistance. Financial support: FAPESP