A Fusion Approach Linking Signaling Logic and Metabolic Mass-Flow Kinetics in Hepatocytes

摘要

Starting from (i) an ODE-based kinetic model, covering metabolic processes and mass-flows in hepatocytes and (ⅱ) a Boolean network, encompassing associated intracellular hormonal signaling and gene-regulatory events, we introduce a new formalism to integrate signal transduction processes, gene regulation, and metabolism. The integrated model was eventually tested for physiologic representativity by in silico simulations, the latter qualitatively addressing and demonstrating the hepatocyte's switch-like behaviour upon nutrient-dependent changes in extracellular insulin and glucagon levels.