Christine Doucette

Biography

B.Sc. (Cell & Molecular Biology), University of Toronto, 2000 Ph.D. (Cell & Systems Biology), University of Toronto, 2007 Post-Doctoral Fellow (Physiology), University of Toronto, 2012 Assistant Professor (Physiology), University of Manitoba, 2012 - present

Research Interest

To determine the physiological role that mitochondrial uncoupling protein 2 (UCP2) plays in the regulation of insulin secretion in response to various metabolic fuels over 24 hours. Since its discovery over 15 years ago, scientists have been trying to discern the physiological function of UCP2 in the pancreatic β cell. At a biochemical level, we know that UCP2 plays a mild uncoupling role in the β cell that has limited impact on ATP production, but has a greater impact on the regulation of mitochondrial ROS signals, which we now know contributes significantly to the control of insulin secretion. Most of what we know about UCP2 function in the β cell and its control of insulin secretion comes from studies of chronic overexpression or chronic knockdown of UCP2 as well as from studies of UCP2 in extreme stress conditions, e.g. long term starvation/fasting, glucolipotoxicity, diabetes and obesity. What we currently do not know is what the role of UCP2 is in the daily control of beta cell function (i.e. in the absence of stress)? When is UCP2 active and inactive on a daily basis and how does this contribute to the regulation of insulin secretion? What controls the expression of UCP2? To determine how ROS signalling contributes to the regulation of insulin secretion in response to various metabolic fuels over a 24-hour cycle We now know that ROS contributes to the control of insulin secretion. We would like to investigate which species of ROS regulates the stimulation and inhibition of insulin secretion and how ROS species production by the mitochondrion is altered by changing fuel sources over a 24-hour period. We would also like to determine the targets of ROS signaling within the insulin secretory pathways. And finally, we are interested in determining how the antioxidant background of the cell contributes to the control of ROS signals and ultimately insulin secretion. For both of these research interests, we plan to define these mechanisms in healthy pancreatic beta cells and then look at how these pathways/mechanisms are altered or interrupted in a diabetic state, mainly using diabetic mouse models.