Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice

Aims: Increased protein O-GlcNAcylation occurs in response to increased availability of glucose and fatty acids and is a hallmark of diabetes. Previous studies have demonstrated an improvement in heart function associated with decreased protein O-GlcNAcylation. Our group has recently demonstrated a capacity for exercise to decrease protein O-GlcNAcylation in the heart of normal mice; however, the impact of such training under diabetic conditions has not been examined. Main methods: Diabetes was induced in mice through injection of streptozotocin. Animals either remained sedentary or were subjected to 6 weeks of swim training protocol. At the end of 6 weeks in vivo cardiac function was assessed and the hearts were harvested for gene expression and Western blotting in relation to O-GlcNAcylation. Key findings: Diabetes resulted in elevated blood glucose relative to non-diabetic mice. Relative to the sedentary diabetic group, the rate of relaxation (Tau) was significantly improved in the exercised group. Western blot analysis revealed an increase in protein O-GlcNAcylation in the diabetic group which was reversed through exercise despite persistent hyperglycemia. No change in the expression of O-GlcNAc transferase (OGT) was noted between sedentary and exercised diabetic mice; however an increase in the expression and activity of O-GlcNAcase (OGA) was apparent in the exercised group. Significance: This study demonstrates the potential for exercise training to decrease intracellular protein O-GlcNAcylation in the heart even under conditions of persistent hyperglycemia associated with diabetes. Our results suggest the beneficial effects of regular aerobic exercise extend beyond simple regulation of blood glucose levels. (c) 2012 Elsevier Inc. All rights reserved.