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notes: Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism Kinetic Model of Human Hepatic Glucose Metabolism Authors Matthias Koenig, Sascha Bulik and Hermann-Georg Holzhuetter Corresponding Author Matthias Koenig matthias.koenig@charite.de Charite Berlin, Computational Systems Biochemistry, Germany Keywords hepatic glucose metabolism; kinetic model; glucose homeostasis; liver 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 excellent 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 hepatic glucose production under hypoglycemia to hepatic glucose utilization under hyperglycemia essential for glucose homeostasis. 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 whole-body 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. Compartments Id Name Dimension Constant SBO GO cyto cytosol 3 Y SBO:0000290 physical compartment GO:0005829 cytosol blood blood 3 Y SBO:0000290 physical compartment GO:0005615 extracellular space mito mitochondrion 3 Y S…
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836773
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836713
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837025
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167775
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167763
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836917
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167391
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167379
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167367
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836701
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836485
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836941
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167451
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167487
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836233
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167463
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167475
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837122
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168207
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836581
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168231
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168183
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168219
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168171
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168195
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836173
type: Compartment
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836953
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167523
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167511
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836221
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167499
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836677
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836185
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837170
type: Reaction
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168543
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168519
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168531
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168555
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168591
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168603
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837050
type: Reaction
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167883
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167859
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167871
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167895
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837086
type: Reaction
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168003
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167967
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167979
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167991
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836833
type: Reaction
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167139
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167103
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167115
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167127
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837062
type: Reaction
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167919
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167907
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837098
type: Reaction
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reactant: 168015
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168015
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168027
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168063
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168039
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168051
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836845
type: Reaction
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167163
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167187
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167151
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167175
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836881
type: Reaction
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167247
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167259
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167271
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167283
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836989
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167631
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167643
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167667
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167655
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168615
type: Reaction
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168627
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836893
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167295
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167307
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167319
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836797
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837110
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168159
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168135
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168099
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168075
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168087
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168147
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168123
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168111
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