Presenter: Weston Elison, College of Life Sciences, Physiology and Developmental Biology
Authors: Kris Weiland, Jared Weiland, Casey Bauchle, Samuel Stephens, Jeffery Tessem
Faculty Advisor: Jeffery Tessem, College of Life Sciences, Nutrition, Dietetics, and Food Science
Institution: Brigham Young University
Type 2 Diabetes (T2D) has become common as life span and obesity have increased. The CDC estimates that 34 million people in the United States have diabetes. In T2D dysfunctional insulin secretion and insulin resistance cause elevated blood glucose concentrations. Insulin resistance and elevated blood glucose have serious long-term consequences including kidney failure, heart disease, and stroke. The pancreatic beta cells regulate blood glucose by releasing insulin as glucose concentrations increase. In T2D the beta cells become less glucose responsive leading to improper insulin secretion. As T2D progresses insulin secretion decreases. Previous research has shown that the transcription factor Nkx6.1 is necessary for proper insulin secretion. Beta cells from T2D patients show decreased expression of Nkx6.1 and several other key transcription factors, indicating that altered expression of these factors may be clinically relevant. Here we show that a beta cell line cultured in elevated glucose for 24 hours shows decreased Nkx6.1 mRNA and protein concentrations. Elevated glucose leads to impaired insulin secretion and increased reactive oxygen species concentrations (ROS). We propose that ROS lead to decreased Nkx6.1 concentrations, which impairs insulin secretion. We present the effects of the ROS scavenger N-acetyl L-cysteine (NAC) on ROS concentrations, Nkx6.1 concentration, and insulin secretion in beta cells treated with elevated glucose for 24 hours. We also show the effects of Nkx6.1 overexpression by adenovirus on beta cell insulin secretion after treatment with elevated glucose. These results demonstrate the role of elevated ROS in beta cells treated with increased glucose and how this relates to decreased insulin secretion in T2D.