Authors: Spencer Paulsen
Mentors: Jeffery Tessem
Insitution: Brigham Young University
Today approximately 537 million adults are living with diabetes. This figure is expected to rise to about 640 million by the year 2030. Metabolic stress is known to drive the development of the disease. The pancreatic β-cell which is responsible for producing and secreting insulin in response to elevated blood glucose concentrations is particularly sensitive to metabolic stressors. Therefore, understanding the molecular character of β-cells is important to curing diabetes. Nkx6.1 is an important β-cell transcription factor critical for proper β-cell development and function. Our lab has shown a potential interaction between Nkx6.1 and PACS1 in β-cells. PACS1 is associated with the Trans-Golgi network and is involved in protein maturation by sending newly synthesized proteins to their intended target inside or outside the cell. We know that insulin is synthesized in the ER and sent to the Golgi for vesicle packaging. We hypothesized that PACS1 helps sort insulin in the Trans-Golgi network, and that interaction with the β-cell transcription factor Nkx6.1 is essential for this process. Therefore, the study of the interaction between Nkx6.1 and PACS1 may provide a greater understanding of diabetes and insulin secretion in β-cells. Here, we present the results of our investigation of the link between Nkx6.1, PACS1, and the Golgi apparatus. We present data validating the Nkx6.1-PACS1 interaction, the cellular location of the interaction, and the effect of changing glucose concentration on this interaction. These results will help deepen our understanding of how the Nkx6.1-PACS1 interaction works to ensure proper β-cell function.