The ability of beta cells to proliferate or expand becomes restricted with advanced age. Understanding the mechanisms that prevent proliferation in adult beta cells and developing strategies to overcome this block is essential for the development of safe and effective therapies to expand beta cell mass in individuals with type 1 diabetes. Dr. Seung Kim and his team had previously described changes that occur with age that lead to the expression of cell cycle inhibitors in beta cells and account for the decline in proliferative capacity. In the present study, Dr. Kim’s group has identified an extracellular signaling pathway that regulates the changes that limit beta cell proliferation in adult beta cells. The group found that expression of a platelet derived growth factor receptor negatively correlated with age in both mouse and human islets and that forced expression of this receptor in aged beta cells was sufficient to “rejuvenate” them – allowing them to proliferate at rates comparable to juvenile beta cells.
Chen, H., Gu, X., Liu, Y. et al. (2011). PDGF signaling controls age-dependent proliferation in pancreatic beta-cells. Nature 478, 349-355.
Ramifications for Individuals with Type 1 Diabetes:
This early stage research demonstrates that signaling through a specific pathway is one of the principle mechanisms that allow young beta cells to proliferate. Although this work suggests strategies that could be exploited to increase the proliferative capacity of adult beta cells, further work will be required to validate the pathway and identify therapeutic targets to achieve this in individuals with type 1 diabetes.
This work was supported, in part, by JDRF.