BIOMD0000000345
type: SBMLModel
rule: metaid_0000097
parameter: metaid_0000040
rule: metaid_0000104
parameter: metaid_0000043
parameter: metaid_0000044
parameter: metaid_0000047
parameter: metaid_0000026
parameter: COPASI13
species: metaid_0000068
parameter: COPASI16
occurs in: http://identifiers.org/taxonomy/9606
rule: metaid_0000076
rule: metaid_0000077
rule: metaid_0000114
species: metaid_0000065
rule: metaid_0000109
is version of: GO:0038016
notes: This model is from the article: Mathematical modeling and analysis of insulin clearance in vivo. Koschorreck M, Gilles ED. BMC Syst Biol. 2008 May 13;2:43. 18477391 , Abstract: BACKGROUND: Analyzing the dynamics of insulin concentration in the blood is necessary for a comprehensive understanding of the effects of insulin in vivo. Insulin removal from the blood has been addressed in many studies. The results are highly variable with respect to insulin clearance and the relative contributions of hepatic and renal insulin degradation. RESULTS: We present a dynamic mathematical model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. The model describes renal and hepatic insulin degradation, pancreatic insulin secretion and nonspecific insulin binding in the liver. Hepatic insulin receptor activation by insulin binding, receptor internalization and autophosphorylation is explicitly included in the model. We present a detailed mathematical analysis of insulin degradation and insulin clearance. Stationary model analysis shows that degradation rates, relative contributions of the different tissues to total insulin degradation and insulin clearance highly depend on the insulin concentration. CONCLUSION: This study provides a detailed dynamic model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. Experimental data sets from literature are used for the model validation. We show that essential dynamic and stationary characteristics of insulin degradation are nonlinear and depend on the actual insulin concentration. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, La…
area units: area
species: metaid_0000066
volume units: volume
rule: metaid_0000093
rule: metaid_0000086
parameter: COPASI11
rule: metaid_0000123
rule: metaid_0000108
parameter: COPASI3
parameter: metaid_0000051
parameter: COPASI6
parameter: metaid_0000029
species: metaid_0000071
parameter: metaid_0000030
parameter: metaid_0000021
parameter: metaid_0000034
occurs in: BTO:0000575
parameter: metaid_0000037
rule: metaid_0000092
rule: metaid_0000085
parameter: metaid_0000061
rule: metaid_0000122
rule: metaid_0000118
rule: metaid_0000117
parameter: metaid_0000041
rule: metaid_0000103
parameter: metaid_0000019
parameter: metaid_0000054
parameter: COPASI9
parameter: metaid_0000045
rule: metaid_0000113
parameter: metaid_0000058
parameter: metaid_0000024
species: metaid_0000074
parameter: metaid_0000027
parameter: COPASI14
species: COPASI2
parameter: metaid_0000048
rule: metaid_0000089
rule: metaid_0000081
species: metaid_0000064
is version of: GO:0005009
parameter: COPASI17
is: MODEL1108040000
rule: metaid_0000082
length unit: length
rule: metaid_0000075
parameter: COPASI12
rule: metaid_0000126
rule: metaid_0000111
parameter: COPASI4
rule: metaid_0000112
rule: metaid_0000107
parameter: metaid_0000031
parameter: metaid_0000032
name: Koschorreck2008_InsulinClearance
parameter: metaid_0000035
rule: metaid_0000091
rule: metaid_0000098
rule: metaid_0000084
rule: metaid_0000099

metaid_0000040
type: Parameter
is: SBO:0000504
constant: false
value: 1.47826086956522
name: mkidney

metaid_0000043
type: Parameter
is version of: GO:0005102
is: SBO:0000009
constant: false
value: 0.0
name: r2

metaid_0000044
type: Parameter
is: GO:0005102
is: SBO:0000009
constant: false
value: 0.0
name: r3

metaid_0000047
type: Parameter
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is: SBO:0000009
constant: false
value: 0.0
name: r6

metaid_0000026
type: Parameter
is: SBO:0000216
constant: true
value: 0.0231
name: kyp

COPASI13
type: Parameter
is: SBO:0000064
constant: false
value: -1.11022302462516E-16
name: ReceptorIns2

metaid_0000068
type: Species
in compartment: metaid_0000062
initial amount: NaN
name: IRp
boundary condition: true
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has only substance units: false
initial concentration: 0.0
is version of: REACT 3057.1

metaid_0000062
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartment1

COPASI16
type: Parameter
is: SBO:0000064
constant: false
value: -1.11022302462516E-16
name: ReceptorInsEN

metaid_0000065
type: Species
boundary condition: true
is: SBO:0000297
has only substance units: false
is version of: REACT 3518.1
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constant: false
initial concentration: 0.0
name: IR
in compartment: metaid_0000062

metaid_0000066
type: Species
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initial concentration: 0.0
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in compartment: metaid_0000062
initial amount: NaN
name: I2R

COPASI11
type: Parameter
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constant: false
value: 1.77516670169197
name: Ctotal

COPASI3
type: Parameter
is: SBO:0000002
constant: true
value: 200.0
name: bw

metaid_0000051
type: Parameter
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constant: false
value: 0.0
name: i3

COPASI6
type: Parameter
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constant: false
value: 4.38312765849869
name: Ratetotal

metaid_0000029
type: Parameter
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constant: true
value: 0.001533
name: reck1

metaid_0000071
type: Species
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initial amount: NaN
name: IRen
occurs in: REACT 599.1
boundary condition: true
constant: false
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metaid_0000030
type: Parameter
is: SBO:0000009
constant: true
value: 40.0
name: Rtotal

metaid_0000021
type: Parameter
is: SBO:0000180
constant: true
value: 0.04
name: kins2d

metaid_0000034
type: Parameter
is: SBO:0000009
constant: true
value: 0.5
name: Kpan

metaid_0000037
type: Parameter
is: SBO:0000226
constant: true
value: 1051.0
name: rholiver

metaid_0000061
type: Parameter
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constant: false
value: 0.0
name: f6

metaid_0000041
type: Parameter
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constant: false
value: 3.32608695652174E-5
name: Kkidney

metaid_0000019
type: Parameter
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constant: true
value: 0.001
name: kins

metaid_0000054
type: Parameter
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constant: false
value: 0.0
name: i6

COPASI9
type: Parameter
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constant: false
value: 1.57560148430067
name: Cliver

metaid_0000045
type: Parameter
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constant: false
value: 0.0
name: r4

metaid_0000058
type: Parameter
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constant: false
value: 0.0
name: f3

metaid_0000024
type: Parameter
is: SBO:0000330
constant: true
value: 0.00385
name: kyd

metaid_0000074
type: Species
initial concentration: 0.0
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constant: false
name: IRPen
boundary condition: true
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is version of: REACT 4836.1

metaid_0000027
type: Parameter
is version of: GO:0038016
is: SBO:0000009
constant: true
value: 5.5E-4
name: intk1

COPASI14
type: Parameter
is: SBO:0000064
constant: false
value: 0.0
name: ReceptorInsPM

COPASI2
type: Species
initial amount: NaN
constant: false
name: I2RPen
is: SBO:0000297
initial concentration: -4.44089209850063E-15
has version: REACT 4836.1
boundary condition: true
has only substance units: false
in compartment: metaid_0000062

metaid_0000048
type: Parameter
is version of: GO:0005102
is: SBO:0000009
constant: false
value: 0.0
name: r7

metaid_0000064
type: Species
is: GO:0016088
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constant: true
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boundary condition: true
initial concentration: 100.0
has only substance units: false
is: P01308
name: ins
initial amount: NaN

COPASI17
type: Parameter
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constant: false
value: -1.11022302462516E-16
name: ReceptorIns2EN

COPASI12
type: Parameter
is: SBO:0000064
constant: false
value: -1.11022302462516E-16
name: ReceptorIns

COPASI4
type: Parameter
is: SBO:0000179
constant: false
value: 3.89037403531029
name: rliv

metaid_0000031
type: Parameter
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is: SBO:0000009
constant: true
value: 0.35
name: k1ub

metaid_0000032
type: Parameter
is: SBO:0000180
constant: true
value: 0.2
name: k2ub

metaid_0000035
type: Parameter
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constant: false
value: 10.0
name: mliver

metaid_0000073
type: Species
is: SBO:0000297
is version of: REACT 3809.1
in compartment: metaid_0000062
initial amount: NaN
constant: false
boundary condition: true
name: RPen
has only substance units: false
initial concentration: 0.0

metaid_0000063
type: Species
is: GO:0005899
boundary condition: true
has only substance units: false
name: R
initial concentration: 35.3837
in compartment: metaid_0000062
is: SBO:0000244
is: P06213
initial amount: NaN
constant: false

metaid_0000052
type: Parameter
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constant: false
value: -1.70974345792274E-17
name: i4

COPASI7
type: Parameter
is: SBO:0000009
constant: false
value: 88.757944974909
name: Fracliver

metaid_0000055
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is: GO:0016310
is: SBO:0000216
constant: false
value: 3.20632409511745E-17
name: i7

metaid_0000056
type: Parameter
is version of: GO:0006897
is: SBO:0000009
constant: false
value: -4.78999999985533E-8
name: f1

metaid_0000022
type: Parameter
is: SBO:0000180
constant: true
value: 0.001925
name: kins1den

metaid_0000059
type: Parameter
is version of: GO:0006897
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constant: false
value: 0.0
name: f4

metaid_0000025
type: Parameter
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constant: true
value: 0.00722
name: kyden

metaid_0000038
type: Parameter
is: SBO:0000468
constant: false
value: 0.00742150333016175
name: vhep

metaid_0000069
type: Species
has version: REACT 3057.1
initial concentration: 0.0
boundary condition: true
constant: false
is: SBO:0000297
has only substance units: false
name: I2Rp
in compartment: metaid_0000062
initial amount: NaN

metaid_0000042
type: Parameter
is version of: GO:0005102
is: SBO:0000009
constant: false
value: 3.53837
name: r1

metaid_0000046
type: Parameter
is version of: GO:0005102
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constant: false
value: 0.0
name: r5

metaid_0000049
type: Parameter
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is: SBO:0000216
constant: false
value: 0.0
name: i1

metaid_0000070
type: Species
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constant: false
boundary condition: true
has only substance units: false
initial concentration: 4.6163
name: Ren
in compartment: metaid_0000062
initial amount: NaN
is: SBO:0000244

COPASI15
type: Parameter
is: SBO:0000064
constant: false
value: 0.0
name: ReceptorIns2PM

COPASI10
type: Parameter
is: SBO:0000009
constant: false
value: 0.199565217391304
name: Ckidney

metaid_0000067
type: Species
boundary condition: true
name: Rp
has only substance units: false
is version of: REACT 4536.1
is: SBO:0000244
in compartment: metaid_0000062
initial amount: NaN
initial concentration: 0.0
constant: false

metaid_0000033
type: Parameter
is version of: GO:0030073
is: SBO:0000009
constant: true
value: 0.0016976
name: pansec

metaid_0000050
type: Parameter
is version of: GO:0016310
is: SBO:0000216
constant: false
value: 0.0
name: i2

metaid_0000072
type: Species
is: SBO:0000297
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000062
name: I2Ren

metaid_0000060
type: Parameter
is: GO:0006897
is: SBO:0000009
constant: false
value: 0.0
name: f5

COPASI5
type: Parameter
is: SBO:0000179
constant: false
value: 0.492753623188406
name: rkid

metaid_0000028
type: Parameter
is version of: GO:0038016
is: SBO:0000009
constant: true
value: 2.0E-4
name: intk2

metaid_0000053
type: Parameter
is part of: GO:0016310
is: SBO:0000216
constant: false
value: 0.0
name: i5

COPASI8
type: Parameter
is: SBO:0000009
constant: false
value: 11.242055025091
name: Frackidney

metaid_0000020
type: Parameter
is: SBO:0000180
constant: true
value: 4.0E-4
name: kins1d

metaid_0000057
type: Parameter
is: GO:0006897
is: SBO:0000009
constant: false
value: 0.0
name: f2

metaid_0000023
type: Parameter
is: SBO:0000180
constant: true
value: 0.00385
name: kins2den

metaid_0000036
type: Parameter
is: SBO:0000468
constant: false
value: 0.00675
name: vp

metaid_0000039
type: Parameter
is: SBO:0000468
constant: false
value: 0.0021216
name: vd

W3 CDTF: Fri Aug 05 10:33:47 BST 2011

ORG:
  orgname: EMBL-EBI
n:
  given: Ishan
  family: Ajmera

W3 CDTF: Fri Mar 09 16:16:46 GMT 2012