The role of Raf-1 in pancreatic beta cell survival and insulin signaling

While we know that Type 1 diabetes is caused by the destruction of insulin-secreting beta-cells in the pancreatic islets, the processes that regulate beta-cell death remain unclear. This has hindered the development of strategies to halt or prevent the development of diabetes. One possible new treatment, islet transplantation, was initially heralded as a promising therapy for Type 1 diabetes because it removed the need of daily insulin injections. However, the transplanted beta-cells were found to gradually die, which resulted in transplant recipients having to resume the use of insulin injections. In order for islet transplantation to be effective, new approaches to promote islet survival are required. In earlier work, Dr. Gareth Lim’s colleagues identified insulin as a critical pro-survival factor for beta-cells. Their findings suggest that secreted insulin from beta-cells may promote self-survival. However, the mechanisms that lead to the beneficial effects of insulin need to be clarified. Consequently, Gareth Lim is currently investigating the mechanisms by which insulin acts on the beta- cell. Specifically, he is doing a series of experiments to show that the protein Raf-1 kinase, which is activated by insulin and has been shown to have an important role in regulating cell death, is essential for beta-cell survival. The results of his studies will improve our understanding of the mechanisms of beta-cell death. They may also lead to novel therapeutic strategies for preventing beta-cell destruction in Type 1 diabetics and their at-risk relatives. Furthermore, an understanding of the pathways involved in beta-cell survival may also lead to new methods to increase the survival of beta-cells after islet transplantation, thereby increasing the effectiveness of this treatment.