The long-term objective of the proposed work is to define the relationship of cardiac myofilament remodelling in streptozotocin-induced diabetic mice to observed functional deficits. To address this objective, the first aim of the study is to clarify the effect of diabetes on the cardiac myofilament function and establish the nature of the remodeling events associated with such effect. In vitro biochemical analysis of cardiac myofilaments isolated from streptozotocin-induced diabetic mice will be performed by determining the calcium sensitivity, an indirect measure of contractile function. In addition, changes in contractile protein isoforms will be determined at protein and RNA levels.
The second aim i s to test the ability of a chronic exercise program to reverse the changes in contractile function and myofilament remodeling. For this purpose diabetic mice will be chronically trained and following the training program, biochemical and molecular analysis will be performed as related to aim 1.
