Presenter: Jared Wieland, College of Life Sciences, Biology
Authors: Jared A Wieland, Jacob Herring, Kristopher L Wieland, Weston Ellison, Jeffery Tessem
Faculty Advisor: Jeffery Tessem, College of Life Sciences, Biology
Institution: Brigham Young University
Prevalence of Type 2 Diabetes (T2D) has increased in recent years with an estimated 422 million cases worldwide. In 2016, 1.6 million deaths were directly caused by diabetes. T2D is a condition characterized by loss of glucose sensitivity throughout the body resulting in dysfunctional insulin secretion in pancreatic beta cells. Extensive research has led to the discovery of many regulatory genes and transcription factors that are necessary for beta cell function. Among these factors, Nkx6.1 is essential to maintain functional beta cell identity by regulating insulin production, insulin secretion, and beta cell proliferation. Preliminary research shows that culturing beta cells for 24 hours in elevated glucose concentrations decreases Nkx6.1 protein and RNA. Increased glucose concentration also decreased glucose stimulated insulin secretion (GSIS) after 72 hours of culture, indicating loss of glucose sensitivity. We hypothesized that the significant decrease of Nkx6.1 levels is caused by increased reactive oxygen species (ROS). To test this hypothesis, Nkx6.1 mRNA and protein levels during high glucose concentrations, with and without treatment of the ROS scavenger N-Acetyl-L-Cysteine (NAC) were measured. We present the effects culture in a hyperglycemic environment with and without ROS scavengers on mRNA and protein levels. Finally, GSIS in beta cells cultured under hyperglycemic conditions with and without NAC is presented. This revolutionary research is essential to understanding the effect of T2D on the beta cell and creating effective safe treatments to increase functional beta cell mass.