Grant: Project Grant

Diabetes is a major health issue in Canada, costing billions of dollars and affecting millions of people. It occurs when the body doesn't produce enough insulin, leading to high blood sugar levels. One potential treatment is transplanting insulin-producing cells, but there are challenges in maintaining their optimal function. One important controller of cellular activity is the Mediator, a molecular machine that helps cells achieve and maintain their identity and function. We are investigating how one Mediator protein, called Med15, influences the development and function of insulin-producing cells in the pancreas, which are crucial in diabetes. By studying mice where Med15 was removed at different stages of cell development, we found that Med15 is important for the maturation and function of cells producing insulin and glucagon, both hormones critical in the development of diabetes. Further experiments showed that Med15 interacts with specific genes and proteins involved in the maturation of the cells producing these hormones. We also found that increasing Med15 levels improved cell function in laboratory-grown insulin-producing cells. Based on these results we hypothesize that Med15 promotes function of pancreatic hormone-secreting cells, throughout life and in conditions of pancreas stress. We will test our hypotheses with the following aims: 1.We will investigate how Med15 affects insulin-producing cells in conditions of stress and after transplantation 2.We will study Med15's role in glucagon-producing cells, both during their development and after they're made 3.We will explore the dynamic regulation of Med15 and of the whole Mediator complex, to better understand its role in the pancreas This research could lead to new ways to improve the function of hormone-producing cells, which could benefit diabetes treatment, including potentially improving the success of stem cell therapies for type 1 diabetes or enhancing insulin production in type 2 diabetes.