Grant: Operating Grant

Type 2 diabetes (T2D) is a global epidemic and an economic burden that affects more than 3 million Canadians. T2D results from malfunction of, damage, or loss of insulin-producing cells of the pancreas, called beta cells. My research focuses on how inflammation causes beta cell malfunction and loss. The main player contributing to islet inflammation in T2D is an immune cell called the macrophage. Macrophages play both detrimental and beneficial roles. I propose to convert the detrimental macrophages found in islets of those with T2D, into beneficial healing and tissue-regenerating macrophages. Our research will facilitate this using 3 distinct approaches. First, we will make regenerative macrophages in a dish and ensure that they improve beta cell survival and function. We will then transfer these macrophages into a mouse and test whether they protect from inflammation and chemically-induced diabetes. In a second set of studies we will determine what substances beneficial macrophages produce to stimulate beta cell regeneration in a mouse. This will inform the future translation of these studies towards people with T2D. Finally, we will make regenerative macrophages in a dish using bone marrow from rodents with type 2 diabetes, and transfer them into these same rodents with type 2 diabetes to reduce inflammation and help regenerate beta cells.