Diabetes is a disease that affects millions of people worldwide and is becoming more prevalent. A hallmark symptom of diabetes is the inability to regulate blood glucose levels after a meal. The Nr4a family of transcription factors regulates the expression of key glucose metabolism genes, and type 2 diabetics have significant decreases in mRNA expression of Nr4a1 and Nr4a3 in the pancreatic islet. Furthermore, Nr4a1KO mice cause decreased beta cell mass and insulin secretion. We have shown that changing media glucose concentrations from 2.5mM to 11mM, a change indicative of a normal postprandial response, is sufficient to induce Nr4a1 and Nr4a3 expression in beta cells. This same change in glucose concentration is responsible for beta cell insulin secretion. We hypothesized that the postprandial induction of the Nr4a's is essential for beta cell glucose sensing and insulin secretion, and that glucotoxic conditions that impair insulin secretion fail to induce Nr4a expression. Here we show how the postprandial Nr4a gene expression affects beta cell glucose stimulated insulin secretion under normal glucose concentrations and glucotoxic conditions to prove this hypothesis.