Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism
Figure 3
HGP, gluconeogenesis (GNG), glycogenolysis (GLY) and GNG/HGP in short term fasting over 70 h.
Experimental data from 25 separately published studies based on a variety of different labeling approaches listed in Table 2 and given in Dataset S1. Simulation time courses (dashed lines) start at t = 10 h with glycogen partially filled glycogen stores (350 mM). Blood glucose is varied between 3.6 mM (red) and 4.6 mM (green) in steps of 0.2 mM. The blue curve corresponds to a situation where the plasma glucose concentration changes over the time of fasting from 4.2 mM to 3.6 mM in 70 h. (A) HGP decreases with increasing fasting time and reaches constant levels after around 25 h. With decreasing blood glucose HGP increases. (B) gluconeogenesis is almost constant over time. With decreasing blood glucose GNG increases (C) glycogenolysis decreases over time with decreasing glycogen. Lower blood glucose results in an initially higher GLY rate (D) GNG/HGP. The relative contribution of gluconeogenesis to the hepatic glucose production increases over time. After 40 h fasting over 90% of the produced glucose comes from de novo synthesis.