Project 174054

Type 2 diabetes affects more than 2 million Canadians, and is a major risk factor for coronary heart disease, the leading cause of death in Canada. Type 2 diabetes results from a relative insufficiency of specific cells in the pancreas ("beta-cells") to produce enough insulin to meet the increasing metabolic demands caused by obesity and ageing. Type 2 diabetes often occurs together with elevated levels of LDL ("bad cholesterol") and low levels of HDL ("good cholesterol"), but the mechanistic connections between cholesterol metabolism and diabetes are poorly understood. We recently discovered that the cholesterol transporter ABCA1, which is crucial for regulating cholesterol levels inside cells, is essential for the normal release of insulin in beta-cells. Mice which lack Abca1 in beta-cells have impaired glucose tolerance due to impaired beta-cell function. The objective of this proposal is to determine the role of ABCA1 in beta-cell function, glucose metabolism and type 2 diabetes. These studies could suggest a novel mechanism for the development of type 2 diabetes and lead to new ways to prevent and treat this disease.