Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Type 1 Diabetes mellitus is a serious disorder that results from the destruction of the insulin secreting cells of the body. The current treatment for this disease consists of the administration of insulin injections. Insulin injections, however, cannot accurately control blood glucose levels in all patients, and may still result in the development of high blood glucose-induced complications. The results of current treatment, therefore, are both painful and costly. In recent years, transplantation of the tissues that contain insulin-secreting cells, known as islet transplantation, has emerged as a long-term treatment for type 1 diabetes. Islet transplantation is able to provide insulin-independence to most recipients, and more importantly, islet transplantation has been shown to improve blood glucose levels when compared to conventional therapies. Despite these advancements, less than 10% of islet transplant recipients remain insulin independent after 5 years, indicating a failure of the transplant. This failure of islet transplants was traditionally attributed to immune-mediated destruction of the transplant, yet the ability of the transplants to fail in the absence of an immune-mediated has been demonstrated. These findings have lead to the suggestion that other factors may be responsible for the failure of the islet transplants. Recently, high blood sugars and fats have been shown to induce islet death and reduce insulin secretion. These factors can increase inflammation, and may be able to induce immune-mediated destruction of the transplant. We plan to determine whether high blood sugars and fats, known as metabolic stress, are required for, or complicit in, the long-term loss of islet transplants. In particular, we will examine which part of the islets are affected by metabolic stress, and identify potential drug targets which could be used pre-, post-, or co-transplantation to delay, or possibly prevent, future islet transplant failure.