Grant: CIHR Fellowship

Over 2.5 million Canadians are currently living with type 2 diabetes (T2D), a highly destructive condition that results in many long-term health complications. Current T2D treatments provide incomplete disease control and cause undesirable side effects, indicating a strong need for new and effective therapies. T2D occurs when the body cannot produce sufficient levels of insulin, a hormone that acts to reduce blood glucose (sugar) levels, or when cells cannot properly utilize available insulin. Within the pancreas, specialized cells (beta cells) produce insulin, and other cells (alpha cells) respond to insulin, and together their actions regulate blood glucose levels. In T2D, both alpha and beta cells become stressed and dysfunctional. This results in decreased insulin levels and action, which results in high blood glucose levels and the onset of disease. The proposed project is focused on preventing or reversing alpha and beta cell stress as an attractive approach to restoring normal pancreatic cell function and preventing T2D. It was recently discovered that the naturally produced molecule interleukin (IL)-22 is a powerful suppressor of pancreatic cell stress. Importantly, IL-22 treatment restores normal blood glucose levels in obese mice; however, the mechanisms and cell types through which IL-22 treatment functions are unknown. The goal of this project is to identify key genetic targets of IL-22 action in pancreatic cells and determine the significance of these targets in the beneficial effects of IL-22. Additionally, by examining mice that are deficient in IL-22 action in alpha or beta cells, and measuring their ability to develop metabolic disease, I will determine which cells mediate the protective effects. Together, these studies will provide fundamental information on the role of IL-22 in health and disease and ultimately will lead to the development of novel therapies for the prevention and treatment of T2D.