AI Article Synopsis
- Circadian rhythms play a crucial role in regulating metabolism at various biological levels, and disruptions can lead to serious health issues like obesity and diabetes.
- A semimechanistic mathematical model was developed to investigate how disruptions in circadian rhythms affect glucose production in the liver, incorporating factors like light-dark cycles and feeding-fasting patterns.
- The model was validated with animal data, and simulations indicated that targeting local pathways associated with feeding-fasting rhythms could help restore normal glucose metabolism in cases of disruption.
Article Abstract
The circadian rhythms influence the metabolic activity from molecular level to tissue, organ, and host level. Disruption of the circadian rhythms manifests to the host's health as metabolic syndromes, including obesity, diabetes, and elevated plasma glucose, eventually leading to cardiovascular diseases. Therefore, it is imperative to understand the mechanism behind the relationship between circadian rhythms and metabolism. To start answering this question, we propose a semimechanistic mathematical model to study the effect of circadian disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark cycle and feeding-fasting cycle as two environmental inputs that entrain the metabolic activity in the liver. The model was validated by comparison with data from mice and rat experimental studies. Formal sensitivity and uncertainty analyses were conducted to elaborate on the driving forces for hepatic gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout suggests that modification to the local pathways tied most closely to the feeding-fasting rhythms may be the most efficient way to restore the disrupted glucose metabolism in liver.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032066 | PMC |
| http://dx.doi.org/10.1152/ajpendo.00271.2017 | DOI Listing |
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