Grant: CIHR Fellowship

Diabetes is an important cause of death and disease currently affecting 2.5 million Canadians. This disease is a characterized by increased levels of glucose in the blood and may lead to several complications including kidney disease, nerve damage, loss of vision and cardiovascular disease. Diabetes is caused by a decrease in sensitivity for insulin, a hormone made by the beta cells in the pancreas that stimulates glucose uptake from the blood. In addition insulin production is decreased in diabetes because of dysfunction and death of the insulin producing beta cells. Interestingly, low blood levels of the good HDL cholesterol is a risk factor for the development of diabetes. HDL has been shown to reduce beta cell death. The mechanism by which HDL protects beta cells is however unknown. HDL interacts with the cholesterol transporter ABCA1, previous studies from our lab have shown that ABCA1 is essential for insulin secretion by the beta cells. Therefore the goal of this proposed study is to evaluate the impact of HDL and ABCA1 in beta cell death and underling mechanisms including inflammation intracellular processes. First, we will use beta cells from mice with and without ABCA1 and incubate them with or without HDL. Inflammation, cell death and levels of intracellular markers that are known to affect cell death will be measured. Secondly, we will use mice with high and low HDL levels in their blood to evaluate how blood levels of HDL affect beta cell function, survival and diabetes development. This project gives insight into the relationship between HDL and diabetes which is essential in the development of novel strategies to prevent and treat diabetes using HDL and ABCA1 as targets.