Combined insulin treatment and intense exercise training improved basal cardiac function and Ca²⁺-cycling proteins expression in type 1 diabetic rats

This study investigated the effects of 8 weeks of intense exercise training combined with insulin treatment on the Ca(2+)-cycling protein complex expression and their functional consequences on cardiac function in type 1 diabetic rat hearts. Diabetic Wistar rats were randomly assigned into the following groups: received no treatment, insulin-treated diabetic, trained diabetic, and trained insulin-treated diabetic. A control group was also included. Insulin treatment and (or) treadmill intense exercise training were conducted over 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac expression of the main Ca(2+)-cycling proteins (RyR2, FKBP 12.6, SERCA2, PLB, NCX1) was assessed by Western blot. Diabetes altered basal cardiac function (±dP/dt) and decrease the expression of the main Ca(2+)-cycling proteins expression: RyR2, SERCA2, and NCX1 (p < 0.05). Whereas combined treatment was not able to normalize -dP/dt, it succeeded to normalize +dP/dt of diabetic rats (p < 0.05). Moreover, both insulin and intense exercise training, applied solely, increased the expression of the Ca(2+)-cycling proteins: RyR2, SERCA2, PLB. and NCX1 (p < 0.05). But this effect was higher when the 2 treatments were combined. These data are the first to show that combined insulin treatment and intense exercise training during diabetes synergistically act on the expression of the main Ca(2+)-cycling proteins, providing insights into mechanisms by which the dual treatment during diabetes improves cardiac function.