Authors: Nathan Vaughan
Mentors: Jeffery Tessem
Insitution: Brigham Young University
Diabetes Mellitus is a chronic disease characterized by a loss of functional beta cell mass, and impaired glucose homeostasis. Elevated glucose levels in the body are known to be the cause of a plethora of debilitating illnesses. Hyperglycemia negatively effects beta cell function, resulting in impaired insulin secretion and cell death. Two key transcription factors involved in beta cell development, function, and proliferation are Nkx6.1 and Pdx1. We have shown a binding interaction between these Nkx6.1 and Pdx1 and have shown that they co-regulate various genes necessary for beta cell maturity and function. Preliminary data indicate that elevated glucose concentrations downregulate Nkx6.1 mRNA and protein, as well as Pdx1 mRNA. However, the effect of elevated glucose concentrations on Pdx1 and Nkx6.1 binding interaction and subsequent function remains largely unexplored. Here we demonstrate the effect of hyperglycemia on the Pdx1-Nkx6.1 interaction, and the effect on expression of Pdx1 and Nkx6.1 downstream target genes. Understanding the effect of hyperglycemia on this interaction will allow us to better understand the stress that a beta cell is under during diabetic conditions, and to develop interventions to ameliorate these effects.