An adult clock component links circadian rhythms to pancreatic β-cell maturation

Abstract

AbstractHow ubiquitous circadian clocks orchestrate tissue-specific outputs is not well understood. Pancreatic β cell-autonomous clocks attune insulin secretion to daily energy cycles, and desynchrony from genetic or behavioral disruptions raises type 2 diabetes risk. We show that the transcription factor DEC1, a clock component induced in adult β cells, coordinates their glucose responsiveness by synchronizing energy metabolism and secretory gene oscillations.Dec1-ablated mice develop lifelong hypo-insulinemic diabetes, despite normal islet formation and intact circadianClockandBmal1activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, andDec1loss disrupts their transcription synchrony. Accordingly, β-cellDec1ablation causes hypo-insulinemia due to immature glucose responsiveness, dampening insulin rhythms. Thus, Dec1 links circadian clockwork to the β-cell maturation process, aligning metabolism to diurnal energy cycles.