Computational modeling and analysis of the impacts of sleep deprivation on glucose stimulated insulin secretion

摘要

Circadian clock is an exquisite internal biological clock functioning in all living organisms. Lifestyle changes such as shift work or frequent travelling might result in malfunctioning of the central and consequently the peripheral clocks leading to different metabolic disorders. Disruptions in beta cell clock have been found to be a potential reason behind beta cell failure that makes a person prone towards developing type 2 diabetes (T2DM). In this study, a Petri net model for beta cell circadian clock has been developed, followed by analysis of the negative impacts of sleep deprivation conditions on the process of glucose stimulated insulin secretion (GSIS) through misalignment of circadian clock. The analysis of structural properties of the Petri net model reveals robustness of the circadian system. The simulation results predict that sleep loss negatively affects the expression of circadian genes which eventually leads to impaired GSIS and beta cell failure. These results suggest that sleep/wake cycle is a vital contributor for the entrainment of the circadian clock and normal functioning of beta cell.