It's What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets

Abstract

Our ever-changing modern environment is a significant contributor to the increased prevalence of many chronic diseases, and particularly, type 2 diabetes mellitus (T2DM). Although the modern era has ushered in numerous changes to our daily living conditions, changes in "what" and "when" we eat appear to disproportionately fuel the rise of T2DM. The pancreatic islet is a key biological controller of an organism's glucose homeostasis and thus plays an outsized role to coordinate the response to environmental factors to preserve euglycemia through a delicate balance of endocrine outputs. Both successful and failed adaptation to dynamic environmental stimuli has been postulated to occur due to changes in the transcriptional and epigenetic regulation of pathways associated with islet secretory function and survival. Therefore, in this review we examined and evaluated the current evidence elucidating the key epigenetic mechanisms and transcriptional programs underlying the islet's coordinated response to the interaction between the timing and the composition of dietary nutrients common to modern lifestyles. With the explosion of next generation sequencing, along with the development of novel informatic and -omic approaches, future work will continue to unravel the environmental-epigenetic relationship in islet biology with the goal of identifying transcriptional and epigenetic targets associated with islet perturbations in T2DM.

Keywords: epigenetics; high-fat diet; intermittent fasting; ketogenic diet; low-protein diet; pancreatic islet; time-restricted feeding; type 2 diabetes mellitus.