Grant: Project Grant

In Canada, almost 11 million individuals live with diabetes or pre-diabetes with heart disease being its leading cause of death. Traditionally, the management of diabetes has focused mainly on controlling high blood glucose levels. Unfortunately, despite heroic efforts to normalize this blood glucose, poor medication management predisposes these patients to heart failure. This is because, in Type 1 diabetes, multiple finger pricks and daily insulin injections (3-4/day) mean poor patient compliance, and variations in blood glucose management that fluctuate from insufficient to poor control. One instigator for the development of heart failure following diabetes is how this organ utilizes different sources of fuel for energy. During diabetes the heart switches from using both sugar and fats, to only fats. This transformation to using fats as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has terrible end results. This is because toxic by-products are produced by overuse of fats, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating fat delivery to the heart, and its function during diabetes has not been completely revealed. In this proposal, the mechanisms by which LPL regulates fuel utilization by the heart during diabetes will be investigated in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, data from this project may assist in drug development that exclusively targets fuel utilization by the heart to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.