Formal Analysis of Impacts of Sleep Disturbances on Circadian Clock and its Role in Increasing Risk of Type 2 Diabetes Mellitus

Abstract

Circadian clock is an exquisite, internal biological clock functioning in all living organisms. These rhythms play a key role in temporal regulation of metabolism to maintain the energy homeostasis. Central clock or the Suprachiasmatic nuclei (SCN) in the hypothalamus is entrained mainly by white light. The SCN further entrains the clocks of the peripheral tissues to maintain their rhythmicity for their normal functioning. Lifestyle changes in the recent years might lead to various disturbances in light/dark or sleep /wake cycle, resulting in malfunctioning of the central and consequently the peripheral clocks. This malfunctioning leads to various metabolic disorders. Disruptions in cell clock have been found to be a potential reason behind cell failure that makes a person prone towards developing Type 2 Diabetes. Shift workers or frequent travelers suffer from changes in their sleep/wake cycle thus disturbing their normal clock oscillations. This further leads to impaired Glucose stimulated insulin secretion (GSIS) and cell failure. The focus of this study is to use formal computational techniques to develop a model depicting that sleep deprivation produces disturbances in the circadian clock consequently leading to a malfunctioning cell. To achieve this goal, a Petri Net model for cell circadian clock has been developed to analyze the negative impacts of sleep deprivation conditions on the process of GSIS through misalignment of circadian clock. The analysis of structural properties of the Petri Net reveals robustness of the circadian system. The simulation results predict that sleep loss negatively vii affects the expression of circadian genes which then eventually leads to impaired GSIS and cell failure. These results suggests that proper sleep is a vital contributor for circadian clock entrainment and normal functioning of cell.