Grant: Operating Grant

Increasing our understanding of beta cell survival mechanisms is critical to the improvement of treatment of type I and type II diabetes. While islet transplantation offers a promising treatment, this approach is limited by graft immune rejection and impaired function and survival of transplanted islets. The switch protein CREB is critical for the long-term survival of insulin-producing islet cells. Loss of CREB function in islet cells leads to islet cell death and to diabetes. We have identified a complex of signaling proteins - those that detect signals from outside the cell and transmit this information within the cell - that control CREB function in islet cells. This complex includes the enzyme MARK2 and a protein called TORC2 which is required to turn CREB on. We hope to establish what contribution MARK2 and TORC2 makes to the control of CREB activity in islet cells, and to determine whether or not drugs that modify TORC2 activity could be used to promote islet cell function and survival. The knowledge gained will be applied to preserve islet cell survival during islet transplantation for children with Type I diabetes, and to improve islet cell function in Type II diabetes patients who display impaired glucose control.