Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism
Figure 4
Glycogen metabolism and hormone perturbations.
(A) Decrease in glycogen during short term fasting over 60 h. Experimental data from [22] (individual data) and [23] (mean data with STD) given in Dataset S1. Simulation time courses (dashed lines) start from filled glycogen stores (500 mM). Blood glucose is varied between 3.6 mM (red) and 5.0 mM (green) in steps of 0.2 mM (black). The blue curve corresponds to a situation where the plasma glucose concentration changes from initially 5 mM to 3.6 mM in 60 h. Higher blood glucose results in a slower decrease in glycogen. (B) Increase in glycogen after a glucose load. Experimental data from [8], [24], [25] given in Dataset S1. Simulation time courses (dashed lines) start from initial glycogen concentration of 200 mM. Blood glucose concentrations are varied between 5.5 mM (red) and 8.0 mM (green) in steps of 0.5 mM (black). The blue line corresponds to 7 mM. Higher blood glucose results in a faster increase in glycogen after a glucose load. (C) Change in HGP and plasma glucose in insulin deficiency. Insulin (blue) and glucagon (red) time courses for an idealized hormone perturbation (left), the experimental data from [27] (middle), and a simulation taking the experimental profile of hormones and glucose utilization into account are shown in the top row. Middle row depicts the time courses of HGP (red) and whole-body glucose utilization GU (black). Bottom row shows the resulting change in plasma glucose as a consequence of the changes in HGP. Insulin deficiency increases HGP relative to GU resulting in an increase in plasma glucose. After insulin normalization HGP decreases and falls below GU due to the increased blood glucose. (D) Changes in HGP during the infusion period (135–200 min) relative to the pre-infusion period (85–135 min) for the simulations and experiments and the various hormone perturbations. Saline infusion (Figure S1) and somatostatin infusion with insulin and glucagon restauration (Figure S5) have no effect on basal HGP. Insulin and glucagon deficiency (Figure S2) and glucagon deficiency alone (Figure S3) decrease HGP relative to basal values. Insulin deficiency increases basal HGP (Figure 4C, Figure S4).