Grant: Operating Grant

The prevalence of diabetes is increasing rapidly across Canada and around the world. If you have diabetes your risk of having a heart attack or stroke is 2-4 fold greater than if you do not have diabetes. In fact, three out of every four people with diabetes will die of heart attack or stroke. The ultimate goals of our research are; 1. To understand why people with diabetics are a greater risk, and 2. To find ways to protect people with diabetes from heart disease. We have established unique cell and animal model systems to help us attain these goals. Using these systems we have recently found that high levels of sugar in the blood (hyperglycemia) can damage to the cells of the blood vessel walls. Specifically, the blood vessel cells take in the glucose and convert it to a compound called glucosamine. It appears that the high level of glucosamine is responsible for the vessel damage. In fact, when we give high levels of glucosamine to a mouse, we can induce atherosclerosis - a major underlying cause of heart attack and stroke. Our results suggest that if we can block the conversion of glucose to glucosamine, or if we can block the effects of glucosamine on the cells, that we can protect the blood vessels from atherosclerosis in our diabetic models. The experiments described in this grant proposal are designed to increase our understanding of this potentially important mechanism in cells and mouse models. We are especially interested in finding new targets that can be used to block disease progression. These studies are important because they are examining new and potentially more effective strategies to treat and/or prevent the cardiovascular complications of diabetes.