The role of ABCA1 and microRNAs in the regulation of beta cell function

Type 2 diabetes currently affects 2.5 million Canadians. Elevated blood cholesterol levels increase the risk of developing diabetes. Scientists are starting to understand the molecular basis of diabetes and have recently discovered that a deficiency of the ABCA1 molecule, a transporter that removes cholesterol from cells, leads to the accumulation of cholesterol in the insulin secreting-beta cells in the pancreas. This cholesterol accumulation leads to impaired insulin secretion and contributes to diabetes. Therefore, influencing the levels of ABCA1 molecules in beta cells may help control both cholesterol and diabetes. The objective of Dr. Nadeeja Wijesekra's research is to discover new ways to regulate ABCA1 levels in beta cells in order to improve beta cell function and survival. Her project involves the use of small molecules called microRNAs to regulate ABCA1 levels in mouse beta cells. She will identify specific microRNAs that regulate ABCA1 levels in beta cells and determine how they influences beta cell function by measuring insulin secretion and changes in cholesterol levels. Furthermore, these microRNAs will be used in diabetic mouse models to assess whether their disease condition can be improved. Since increased ABCA1 has been shown to have a positive impact on beta cell function, finding ways to increase ABCA1 levels in these cells may be helpful in ameliorating beta cell defects present in diabetes. Thus these studies are the first to outline a therapeutic strategy to modulate cholesterol in beta cells in order to improve whole body glucose homeostasis.