Epigenetic Regulation of Islet Development and Regeneration

Abstract

The incidence of diabetesDiabeteshas registered an exponential increase in the past few decades. Significant efforts have therefore been invested toward understanding of glucose metabolism in human body. To ameliorate the rate of incidence and the effects of diabetes, studies are directed toward lifestyle intervention including diet change in addition to the extensive research in the therapeutic approaches toward the disease. The replenishment of the lost mass and function of the $β$-cells of pancreatic islets that secrete insulin, the key hormone in glucose homeostasis, is under intense investigation. In recent years, considerable understanding of the transcription factor network regulating islet function has been achieved. Epigenetic regulationEpigenetic regulation, a recently investigated aspect of the cellular reprogramming, has emerged as a new paradigm. Indeed, epigenetic mechanisms, including DNA methylationDNA methylation, histone modifications, and non-coding RNA expression, were recently shown to be involved in the control of endocrine cell fate decision, islet differentiation, $β$-cell$β$-cellidentity, proliferation, and mature function. Emerging knowledge regarding mechanisms involving epigenetic regulation suggests that these might be involved in $β$-cell dysfunction and etiology of diabetes. Better understanding of the epigenetic landscapes of islet differentiation and function holds tremendous potential toward improvement of $β$-cell differentiation protocols and discovery of novel therapeutic targets for prevention and treatment of diabetesDiabetes. In this chapter, we discuss the fundamentals of islet developmentEpigenetic regulationof islet developmentand regenerationEpigenetic regulationof regenerationwith special emphasis on $β$-cell proliferation and reprogramming. We then focus on the role of transcription factor networks and epigenetic mechanisms in islet development. Recent trends in in vitro and in vivo regeneration of $β$-cells and insulin production are also discussed.