A composite computational model of liver glucose homeostasis. II. Exploring system behaviour

Area of Science:

• Physiology
• Computational Biology
• Systems Biology

Background:

• Glucose homeostasis is a complex physiological process vital for maintaining stable blood sugar levels.
• Understanding the dynamics of glucose regulation is crucial for metabolic health and disease management.

Purpose of the Study:

• To investigate the behavior of the glucose homeostasis system under varying liver insulin sensitivity and dietary glucose intake.
• To identify critical parameters and dynamic behaviors associated with efficient and failing homeostatic control.

Main Methods:

• Development and utilization of a composite model of the glucose homeostasis system, comprising seven interconnected submodels.
• Analysis of model responses to variations in liver insulin sensitivity and dietary glucose variability.
• Application of bifurcation analysis to identify dynamic phenomena such as stable limit cycles.

Main Results:

• The model successfully replicates published experimental findings in glucose homeostasis.
• Identified bounded parameters defining the region of efficient homeostasis.
• Demonstrated the existence of an optimal insulin sensitivity for effective homeostatic control.
• Highlighted the significance of transient and oscillatory behaviors in characterizing homeostatic failure.

Conclusions:

• The composite model provides valuable insights into glucose homeostasis dynamics.
• Specific levels of liver insulin sensitivity and dietary glucose variability are critical for maintaining metabolic balance.
• The presence of stable limit cycles, identified via bifurcation analysis, signifies potential homeostatic failure.