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

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 ß cell clock have been found to be a potential reason behind ß cell failure that makes a person prone towards developing type 2 diabetes (T2DM). In this study, a Petri net model for ß 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 ß cell failure. These results suggest that sleep/wake cycle is a vital contributor for the entrainment of the circadian clock and normal functioning of ß cell.

Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth.

Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.