Grant: Project Grant

Diabetes mellitus ('diabetes') is a disease where sugar levels in the blood are higher than normal, which damages cells and organs (eyes, kidneys, etc). High blood sugar levels happen because the body cannot produce enough or respond normally to the hormone insulin, which controls blood sugar levels. Currently, roughly 10% of Canadians and over 400 million people worldwide suffer from diabetes. In 2017, the diagnosis and management of diabetes and its associated conditions (e.g. blindness, cardiovascular disease, kidney disease) incurred an estimated global cost of US$ $327 billion, making it a health care priority. Type 1 diabetes (T1D) occurs when the ß-cells of the pancreas, which produce insulin, are lost. Type 2 diabetes (T2D) occurs when the ß-cells don't produce enough insulin to control blood sugar levels. Pancreas and ß-cell development and function are controlled by a network of proteins called transcription factors. One of the most important transcription factors is the so-called Mediator, but its role in the pancreas and ß-cells has never been studied before. We have generated mice that lack one component of Mediator in the ß-cells. These mice develop diabetes because they are unable to produce or maintain enough mature, functional ß-cells. We propose to further characterize these animals to better understand how Mediator regulates the development and function of the pancreas, and how Mediator acts to prevent diabetes. In addition, we propos to test whether genetically enhanced Mediator function results in "better" ß-cells, which could then be used for cell transplantation therapy in diabetic patients. Thus, our research may help design effective treatments for T1D and T2D.