Adam Wynn, Brigham Young University
Nearly 1 in 10 Americans suffer from type 2 diabetes (T2D), a disease that was the 7th leading cause of death in the United States in 2015. A key component in finding a cure for T2D is the pancreatic β-cell, which is responsible for producing and secreting insulin and monitoring blood glucose levels. T2D is characterized by a loss in functional β-cell mass, resulting in decreased insulin secretion and glucose utilization. The orphan nuclear receptor Nr4a1 (Nur77) has well-defined roles throughout the body, specifically with fuel utilization in liver, muscle, and adipose tissues. It’s role in the β-cell, however, is poorly defined. Our data suggests that Nr4a1 plays a critical role in maintaining β-cell mass, secreting insulin, and metabolizing glucose. Our data suggests that Nr4a1 is downregulated during T2D progression due to hyperglycemia and hyperlipidemia. In order to test these hypotheses, we have exposed Cre-mediated Nr4a1 knockout (KO) mice and wild-type (WT) mice to a high-fat diet (causing hyperglycemia) or a low-fat diet (maintaining euglycemia). We will present data showing the effects of Nr4a1 deletion in a high-fat environment on blood glucose levels and weight for both infant and adult mice. These data serve as a step toward understanding the pathway of T2D progression and finding a cure.