Mechanisms underlying protective effects of HDL and ABCA1 in beta cell survival

Diabetes is a major cause of disease and death in BC. According to a report from the Canadian Diabetes Association, 7 percent of BC residents currently have a diagnosis of diabetes, and this number is expected to rise to more than 10 percent by 2020, by which time diabetes-associated heath care costs in BC are expected to rise to $1.9 billion per year. Diabetes and cardiovascular disease are intimately related, and having one of these diseases is a strong risk factor for the other. Altered blood cholesterol levels increase the risk of developing both cardiovascular disease and diabetes. Blood cholesterol is carried in two types of particles: low density lipoprotein (LDL) particles and high density lipoprotein (HDL) particles. The HDL is known as the “”good”” cholesterol, as it removes excess cholesterol from tissues and is therefore considered to be protective in the development of cardiovascular disease and diabetes, and people with low levels of the good HDL cholesterol have an increased risk to develop these diseases. Dr. Willeke de Haan is working to understand how these diseases are related at the molecular level. She is specifically examining the interaction between HDL and two cholesterol transporters, ABCA1 and ABCG1. Previous studies have shown that ABCA1 and ABCG1 are both involved in insulin secretion in cells of the pancreas; this provides insight into how HDL cholesterol influences and may contribute to diabetic metabolism. Her research involves both cultured beta cells, a type of cell that secretes insulin from the pancreas, as well as various mouse models of diabetes. Using these models, Dr. de Haan will determine how altering HDL cholesterol levels contributes to diabetes development by analyzing inflammation, stress, death and markers for underlying mechanisms. Her work will also provide essential insights about the function of HDL, ABCA1 and ABCG1 in the development of diabetes and cardiovascular disease, and will validate these molecules as potential targets in the development of novel therapeutic approaches to these diseases.