Insulin secretion by pancreatic β cells is a dynamic and highly regulated process due to the central importance of insulin in enabling efficient utilization and storage of glucose. Multiple regulatory layers enable β cells to adapt to acute changes in nutrient availability as well as chronic changes in metabolic demand. While epigenetic factors have been well established as regulators of chronic β cell adaptations to insulin resistance, their role in acute adaptations in response to nutrient stimulation has been relatively unexplored. In this issue of the JCI, Wortham et al. report that short-term dynamic changes in histone modifications regulated insulin secretion and acute β cell adaptations in response to fasting and feeding cycles. These findings highlight the importance of investigating whether other epigenetic mechanisms may contribute to acute physiologic adaptations in β cells.