Exercise training suppresses Mst1 activation and attenuates myocardial dysfunction in mice with type 1 diabetes.

Abstract

Our study was to test the effects of aerobic exercise on myocardial function in mice with type 1 diabetes and investigate the underlying mechanism associated with mammalian sterile 20-like kinase 1 (Mst1). Wild-type mice and Mst1(-/-) mice were injected with streptozotocin to induce diabetes and given moderate-intensity exercise for 12 weeks. Phosphorylation of Mst1 was significantly enhanced in the left ventricles of diabetic mice, which was reversed by exercise training. Exercise training or Mst1 deficiency improved myocardial function and reduced myocardial fibrosis in diabetic mice. Exercise training or Mst1 deficiency reduced TUNEL-positive cells and caspase-3 activity in the myocardium of diabetic mice. Exercise training or Mst1 deficiency abated oxidative stress and reduced mitochondrial reactive oxygen species formation, attenuated mitochondrial swelling, and enhanced mitochondrial adenosine triphosphate formation and mitochondrial membrane potential in the myocardium of diabetic mice. Exercise training or Mst1 deficiency suppressed inflammation in the myocardium of diabetic mice. Furthermore, exercise training did not provide further protection in Mst1 knockout mice in diabetes. In conclusion, chronic exercise training attenuated myocardial dysfunction in mice with type 1 diabetes, at least in part, through suppressing Mst1 activation.