Table S1: Global parameter set of the GIM model

Parameter / Value / Dim. / Description / Sourcea
Pharmacokinetic Parameters: Insulin
/ 0.218 / [-] / Lipophilicity / 1
/ 5808 / [g/mol] / Molar Weight / 1
/ 10 / [-] / Renal clearance as a multiple of glomerular filtration rate / Fit
Pharmacokinetic Parameters: Glucose
/ -2.5 / [-] / Lipophilicity / 1
/ 180 / [g/mol] / Molar Weight / 1
/ 0 / [-] / Renal clearance as a multiple of glomerular filtration rate (Renal clearance modeled by a reabsorption function instead 2) / 2
Pharmacokinetic Parameters: Glucagon
/ -1.197 / [-] / Lipophilicity / 1
/ 3483 / [g/mol] / Molar Weight / 1
/ 10 / [-] / Renal clearance as a multiple of glomerular filtration rate / Fit
Hexokinase (Concentrations Recalculated from basal rates in 2)
/ 0,2 / [mmol/l] / Concentration of half max. rate of intracellular glucose metabolization / Fit
/ 267 / [1/min] / Max. rate of metabolization / Fit
Passive Organ / 0.029 / [µmol/l] / Intracellular enzyme concentration / Recal2
Fat / 0.016 / [µmol/l] / Intracellular enzyme concentration / Recal2
Muscle / 0.0214 / [µmol/l] / Intracellular enzyme concentration / Recal2
Liver / 0.272 / [µmol/l] / Intracellular enzyme concentration / Recal2
Brain / 1.05 / [µmol/l] / Intracellular enzyme concentration / Recal2
RBC / 0.082 / [µmol/l] / Intracellular enzyme concentration / Recal2
Threshold Functions
/ 1.33 / [-] / Rate at zero substrate concentration / Refit 2
/ 3 / [-] / Rate at zero substrate concentration / Fit
/ 0.14 / [-] / Rate at zero substrate concentration / Fit
/ 0 / [-] / Rate at zero substrate concentration / Fit
/ 0.7 / [-] / Rate at zero substrate concentration / Fit
/ -1.33 / [-] / Max. change in transporter rate / Refit 2
/ -2.95 / [-] / Max. change in transporter rate / Fit
/ 2.69 / [-] / Max. change in transporter rate / Fit
/ 5 / [-] / Max. change in transporter rate / Fit
/ 18 / [-] / Max. change in transporter rate / Fit
/ 1.45 / [-] / Concentration of half max. rate / Refit 2
/ 0.78 / [-] / Concentration of half max. rate / Fit
/ 1.52 / [-] / Concentration of half max. rate / Fit
/ 1.41 / [-] / Concentration of half max. rate / Fit
/ 4 / [-] / Concentration of half max. rate / Fit
/ 3 / [-] / Hill/cooperativity exponent / Refit 2
/ 3 / [-] / Hill/cooperativity exponent / Fit
/ 1.8 / [-] / Hill/cooperativity exponent / Fit
/ 4 / [-] / Hill/cooperativity exponent / Fit
/ 3 / [-] / Hill/cooperativity exponent / Fit
/ 5750 / [µmol/l] / Basal cellular hepatic glucose / Refit 2
/ 2e-5 / [µmol/l] / Basal interstitial hepatic glucagon / Refit 2
/ 4500 / [µmol/l] / Basal interstitial pancreatic glucose / Refit 2
/ 1,4e-4 / [µmol/l] / Basal interstitial pancreatic insulin / Refit 2
Sensitivities
/ 1 / [-] / Insulin Responsiveness / Default
/ 0.7 / [-] / Glucose Responsiveness / Fit
/ 1 / [-] / Glucagon Responsiveness / Default
/ 1 / [-] / Insulin Sensitivity / Default
/ 1 / [-] / Glucose Sensitivity / Default
/ 1 / [-] / Glucagon Sensitivity / Default
GLUT4
/ 0.0037 / [1/mg] / Rate constant scaling factor / Fit
/ 35 / [mg/min] / Basal peripheral glucose uptake / 2
/ 8 / [mmol/l] / Concentration of half max. rate / 3
/ 3.36 / [µmol/l] / Total muscular transporter concentration / Recalc.2, 4
/ 3,72 / [µmol/l] / Total fat transporter concentration / Recalc.2, 4
GLUT3
/ 1000 / [1/min] / Catalytic rate constant / Fit
/ 3 / [mmol/l] / Concentration of half max. rate of transport from plasma to intracellular / 3
/ 3 / [mmol/l] / Concentration of half max. rate of transport from intracellular to plasma / 3
/ 8.5 / [µmol/l] / Concentration of cerebral transporter expression / Fit
GLUT2
/ 10 / [1/min] / Catalytic rate constant / Fit
/ 17 / [mmol/l] / Concentration of half max. rate of transport from interstitial to intracellular / 3
/ 17 / [mmol/l] / Concentration of half max. rate of transport from intracellular to interstitial / 3
/ 0.55 / [µmol/l] / Concentration of hepatic transporter expression / Fit
/ 2.22 / [µmol/l] / Concentration of transporter expression in the small intestine duodenum / Fit
/ 6.15 / [µmol/l] / Concentration of transporter expression in the small intestine upper jejunum / Fit
/ 1.82 / [µmol/l] / Concentration of transporter expression in the small intestine upper ileum / Fit
/ 1.79 / [µmol/l] / Concentration of transporter expression in the small intestine lower jejunum / Fit
/ 0.57 / [µmol/l] / Concentration of transporter expression in the small intestine lower ileum / Fit
SGLT1
/ 40 / [1/min] / Catalytic rate constant / Fit
/ 0,2 / [mmol/l] / Concentration of half max. rate of transport from lumen to intracellular / 3
/ 2.22 / [µmol/l] / Concentration of transporter expression in the small intestine duodenum / Fit
/ 6.15 / [µmol/l] / Concentration of transporter expression in the small intestine upper jejunum / Fit
/ 1.82 / [µmol/l] / Concentration of transporter expression in the small intestine upper ileum / Fit
/ 1.79 / [µmol/l] / Concentration of transporter expression in the small intestine lower jejunum / Fit
/ 0.57 / [µmol/l] / Concentration of transporter expression in the small intestine lower ileum / Fit
Clearance of glucagon
/ 100 / [l/µmol/min] / Glucagon receptor binding affinity / Fit
/ 0 / [1/min] / Rate constant of glucagon recycling / Fit
/ 0.01 / [1/min] / Rate constant of GPCR recycling / Fit
/ 1e-5 / [µmol/l] / Total concentration of hepatic GPCR / Fit
/ 2 / [1/min] / Intrinsic plasma clearance / Fit
a The table includes, besides the fitted values, parameter values taken from literature. A large share was either recalculated (“Recal.”, i.e. organ glucose metabolization was distributed over the larger number of organs, but remained the same in total) or refitted (“Refit”., this was only done for the threshold functions when transferred from tanh-functions to Michaelis-Menten functions) from Sorensen 2.
1. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, et al. DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res 2011, 39(Database issue): D1035-1041.
2. Sorensen JT. A Physiologic Model of Glucose Metabolism in Man and its Use to Design and Assess Improved Insulin Therapies for Diabetes. PhD thesis, MIT, 1985.
3. Zierler K. Whole body glucose metabolism. Am J Physiol 1999, 276(3 Pt 1): E409-426.
4. Sedaghat AR, Sherman A, Quon MJ. A mathematical model of metabolic insulin signaling pathways. Am J Physiol Endocrinol Metab 2002, 283(5): E1084-1101.