Kformula

Kinetic Model of Hepatic Glucose Metabolism


Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical
model of human hepatic glucose metabolism is lacking so far. Here we present a
detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in
human hepatocytes integrated with the hormonal control of these pathways by insulin,
glucagon and epinephrine. Model simulations are in good agreement with experimental
data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen
metabolism to hepatic glucose production and hepatic glucose utilization under varying
physiological states. (ii) the time courses of postprandial glycogen storage as well as
glycogen depletion in overnight fasting and short term fasting (iii) the switch from net
hepatic glucose production under hypoglycemia to net hepatic glucose utilization under
hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic
glucose metabolism. Response analysis reveals an extra high capacity of the liver to
counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above
7.5 mM (hyperglycemia). Our model may serve as an important module of a wholebody
model of human glucose metabolism and as a valuable tool for understanding the
role of the liver in glucose homeostasis under normal conditions and in diseases like
diabetes or glycogen storage diseases.

Matlab Code reproducing the results is available from
https://github.com/matthiaskoenig/glucose-model
git clone https://github.com/matthiaskoenig/glucose-model

3 items (and an image) are associated with this Model: view in large icon

Filename Format Size Action
Koenig2014_Hepatic_Glucose_Model_annotated.xml XML document 199 KB Download
Koenig2014_Hepatic_Glucose_Model.cps XML document 254 KB Download
Koenig2012_Figure_1.tif TIFF image 1.97 MB Download

Organism: Homo sapiens

Model type: Ordinary differential equations (ODE)

Model format: SBML

Execution or visualisation environment: Copasi

Model image: (Click on the image to zoom)

help Contributors

[Matthias König] [Sascha Bulik] [Hermann-Georg Holzhütter]

help Attributions

None

help Scales


Views: 1455    Downloads: 935
  • Created: 14th Mar 2012 at 00:59
  • Last updated: 16th Feb 2017 at 12:12
  • Last used: 19th Oct 2017 at 09:21

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