Circadian control of islet function

Abstract

Circadian clocks are evolutionarily conserved from single-celled organisms all the way to humans. These oscillators generate rhythms in gene expression and in physiological processes in cells and organisms that maintain a ~24 h periodicity to coincide with the light and dark cycles generated by the earth’s rotation around its own axis. These clocks are self-sustaining and entrainable by external cues. They are generated by transcriptional and translational auto-feedback loops present in every cell. The suprachiasmatic nucleus (SCN) of the hypothalamus forms the central clock and is the pacemaker in mammalian systems. This synchronizes all the peripheral clocks present in other tissues and cells via neurohumoral pathways. Disruption of this circadian rhythm, most notably with shift work, has been associated with many pathophysiological processes and disease states in humans, including diabetes. Disruption of the circadian clock, either by environmental or by genetic disruption, has been shown in rodent models to result in significant β-cell dysfunction. Tissue-specific deletion models of the core clock genes have demonstrated convincingly the critical regulatory role and cell-autonomous function of the molecular clock in β-cells function. Understanding these regulatory pathways and applying them to prevent human disease remain the objective of circadian biology.