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

bioRxiv [Preprint]. 2023 Aug 11:2023.08.11.552890. doi: 10.1101/2023.08.11.552890.

Abstract

How 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 circadian Clock and Bmal1 activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, and Dec1 loss disrupts their transcription synchrony. Accordingly, β-cell Dec1 ablation 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.

Publication types

  • Preprint