Jensen, Daelin; Baxter, Melanie (Brigham Young University)
Faculty Advisor: Tessem, Jeffery (Nutrition, Dietetics, and Food Science; Life Sciences)
Approximately 1.25 million people are currently living with type 1 diabetes. By 2050, 5 million people are expected to be diagnosed with the disease1. The insulin secreting pancreatic beta cells are essential to control proper glucose absorption and storage in insulin sensitive peripheral tissue. Both type 1 and type 2 diabetes are characterized by decreased functional beta cell mass and, consequently, decreased insulin production. One potential intervention is the use of beta cell transplantation from cadaveric donors. A major impediment to greater application of this treatment is the scarcity of transplant ready beta cells. Increasing the quantity of functional beta cells for transplantation will lead to increased insulin production and better management of the disease. Various genes have been defined that can induce beta cell replication. A major caveat of these findings, however, is that these factors induce replication in young beta cells but not in aged beta cells. Age-dependent morphological changes in the beta cell are poorly understood, despite its relevance to type 1 diabetes: here, we show that insulin-positive tissue area changes with age. Given that the majority of beta cells that will be used for transplant will come from aged donors, it is imperative to understand why aged beta cells are refractory to the aforementioned proliferative mechanisms. The cell cycle is tightly regulated by cyclin-dependent kinases. Cyclin-dependent kinase inhibitors (CDKI's) bind to cyclin dependent kinases, inhibiting cell proliferation. We hypothesized that these CDKIs are responsible for the observed lack of proliferation in aged animals. We demonstrate the expression of the Ink4 and Cip/Kip family of CDKI's by mRNA, protein and histological expression in 5 week and 5 month old primary rat beta cells. In addition, we show how size-related expression differences of CDKIs relate to beta cell proliferation.