Papel preventivo do exercício físico nas alterações observadas na via de sinalização insulínica induzidas pela Dexametasona

Abstract

Peripheral insulin resistance is the major side effect after chronic dexamethasone (Dexa) treatment, which is widely used to control inflammatory diseases. On the other hand, exercise training increases insulin-dependent muscle glucose uptake and attenuates hyperglycemia and hyperinsulinemia induced by Dexa treatment. This study investigated whether exercise can modulate the insulin-dependent glucose uptake pathway in order to attenuate the peripheral insulin resistance induced by Dexa treatment. Eighty rats were distributed into 4 groups: sedentary control (SC), sedentary treated with Dexa (SD; 1 mg/kg per day, i.p.), trained control (TC) and trained treated with Dexa (TD). These rats underwent a training period where they were either submitted to a running protocol (60% of physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent Dexa treatment (10 days) concomitant with training. Body weight was measured weekly before treatment and daily during the treatment. Blood glucose was measured at the beginning, after five days and at the end of experimental protocol (one touch ultra test). An ipGTT was performed at the end of the experimental period. After an overnight fast, the rats were anesthetized. After collection of an unchallenged sample (time 0), a solution of 50% glucose (2.0 g/kg body weight) was administered into the peritoneal cavity. Blood samples were collected from the tail at 30, 60, 90 and 120 min for determination of glucose concentrations and calculations of the area under the glucose curve (AUC). The western blot technique was performed to identify IRS-1, PKC-α and p-AKT protein expression in the tibialis anterior (TA) muscle. During the training period, the increase of body weight was similar among the groups. Dexa treatment body weight and exercise did not attenuate this reduction. Exercise training did not alter fasting blood glucose. Dexa treatment significantly increased glycemia in both groups, sedentary animals (SD = +157%) and trained animals (TD = +98%). However, training attenuated this increase since TD was 22% lower than SD groups. The AUC was 39% higher for Dexa-treated rats, but exercise attenuated this peripheral insulin resistance. Dexa significantly reduced IRS-1 (-58%), PKC-α (-44%) and p- AKT (-48%) protein expression in the TA muscle. Moreover, exercise per si increased protein expression of IRS-1 (112%), PKC- α (17%) and p-AKT (93%). Also, exercise blocked these protein expression reductions after Dexa treatment. These results demonstrates for the first time that exercise training can prevent the reductions of IRS-1, p-AKT and PKC- α protein expressions induced by Dexa in the skeletal muscle. Therefore, exercise may be a good strategy to prevent dexamethasone-induced peripheral insulin resistance. Financial support: FAPESP