Grant: China-Canada Joint Health Research Initiative

The common underlying cause for type 1 and type 2 diabetes is the deficiency of pancreatic beta-cell. Beta-cells were once thought to be non-proliferative cells; however it is now well appreciated that these cells indeed maintain the proliferative potential in response to increased insulin demand resulting from metabolic disorders. Therefore, evaluation of cell cycle regulation in Beta-cells is essential for better understanding of pathogenesis and prevention of diabetes. b) Objective of the research proposal Our objective is to define the essential role of the tumour suppressor retinoblastoma (Rb) protein and its family member, p107 that govern cell cycle and cell death in pancreatic beta-cells. We have investigated the role of Rb and p107 in pancreatic beta-cells through mouse model experiments. Mice without the expression of Rb in beta-cells lead to enhanced cell number and improved the insulin secretory response when confronting blood glucose change, which indicates loss of Rb in beta-cells can have a beneficial role in promoting beta-cell growth and cell function. Interestingly, mice with combined loss of Rb and p107 in beta-cells exhibit an unexpected decline in cell number. We wish to further explore the role of Rb proteins in the regulation of beta-cell proliferation and function. This project will lead to a better understanding of the biology of pancreatic beta-cell that plays an important role in the development of diabetes, leading to new strategies for prevention and treatment of diabetes.