Abstract 20528: Exercise Improves Diabetic Heart Performance by Reducing the Levels of Diacylglycerol
Cardiac dysfunction occurs in a substantial proportion of the population with type 1 diabetes through a process of hyperglycemia-induced increase in diacylglycerol (DAG) levels and subsequent activation of protein kinase C βII (PKC-βII). Exercise training attenuates poor cardiovascular performance in type 1 diabetes. In this study, we hypothesized that exercise training modulates cardiac PKC-βII signaling, to elicit its benefits on the diabetic heart. BioBreeding Diabetes Resistant rats, a model of autoimmune type 1 diabetes, were randomly assigned to 4 groups (n=8/group): 1) non-diabetic (control), 2) diabetic, 3) exercised non-diabetic, and 4) exercised diabetic. Exercise training began at diabetes onset. At the end of 8 weeks of diabetes, steady state left ventricular hemodynamic assessment revealed compromised cardiac function in diabetes. Specifically, a 48% decrease in the stroke volume, an 18% decrease in the ejection fraction, and a 51% decrease in the left ventricular output were observed in diabetic group compared to control. Exercise training alleviated these changes. While both +dP/dt and -dP/dt decreased with diabetes (30% and 46%, respectively), compared to control, exercise was able to improve the +dP/dt. Left ventricular collagen fractional area was increased 1.4 fold in diabetic group compared to control, and was returned to the control levels in the exercised diabetic group. The above physiological and anatomical evaluations showed that exercise training was able to prevent the deterioration of left ventricular function and structure in diabetes. To determine a possible mechanism, PKC-βII protein levels and in vitro activity were analyzed and no changes were found with diabetes. Further, molecules involved in PKC-βII signaling were studied. Levels of DAG, a PKC-βII activator, increased with diabetes and exercise training prohibited that increase, returning DAG to control levels. No changes were observed in the levels of sphingosine, a PKC-βII inhibitor, with diabetes or exercise. These results suggest that exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in DAG levels.
- © 2010 by American Heart Association, Inc.