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
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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.
