metaid_0000015
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V1c
type: Species

metaid_0000068
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: measanna
type: Species

metaid_0000011
boundary condition: true
in compartment: metaid_0000003
has only substance units: false
initial amount: 10.0
name: X
constant: false
is: SBO:0000240
is version of: FMA:74531
type: Species
initial concentration: NaN
is version of: CHEBI:36080

metaid_0000021
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: Vm2
type: Species

metaid_0000025
is: SBO:0000009
constant: true
value: 0.012452744
name: k1abasic
type: Parameter

metaid_0000031
is: SBO:0000009
constant: true
value: 1.6722503302
name: k21
type: Parameter

BIOMD0000000343
parameter: metaid_0000029
volume units: volume
species: metaid_0000016
parameter: metaid_0000037
species: metaid_0000017
length unit: length
rule: metaid_0000049
rule: metaid_0000051
rule: metaid_0000045
rule: metaid_0000060
rule: metaid_0000050
species: metaid_0000066
type: SBMLModel
parameter: metaid_0000027
rule: metaid_0000075
rule: metaid_0000071
parameter: metaid_0000024
species: metaid_0000065
parameter: metaid_0000031
species: metaid_0000013
occurs in: http://identifiers.org/taxonomy/9606
substance units: substance
parameter: metaid_0000035
species: metaid_0000023
species: metaid_0000006
curated: true
rule: metaid_0000059
parameter: metaid_0000032
parameter: metaid_0000038
rule: metaid_0000058
name: Brannmark2010_InsulinSignalling_Mifamodel
rule: metaid_0000054
species: metaid_0000005
rule: metaid_0000048
rule: metaid_0000044
species: metaid_0000012
rule: metaid_0000073
rule: metaid_0000063
is part of: GO:0008286
rule: metaid_0000072
notes: This model is from the article: Mass and information feedbacks through receptor endocytosis govern insulin signaling as revealed using a parameter-free modeling framework. Brannmark C, Palmer R, Glad ST, Cedersund G, Stralfors P. J Biol Chem. 2010 Jun 25;285(26):20171-9. 20421297 , Abstract: Insulin and other hormones control target cells through a network of signal-mediating molecules. Such networks are extremely complex due to multiple feedback loops in combination with redundancy, shared signal mediators, and cross-talk between signal pathways. We present a novel framework that integrates experimental work and mathematical modeling to quantitatively characterize the role and relation between co-existing submechanisms in complex signaling networks. The approach is independent of knowing or uniquely estimating model parameters because it only relies on (i) rejections and (ii) core predictions (uniquely identified properties in unidentifiable models). The power of our approach is demonstrated through numerous iterations between experiments, model-based data analyses, and theoretical predictions to characterize the relative role of co-existing feedbacks governing insulin signaling. We examined phosphorylation of the insulin receptor and insulin receptor substrate-1 and endocytosis of the receptor in response to various different experimental perturbations in primary human adipocytes. The analysis revealed that receptor endocytosis is necessary for two identified feedback mechanisms involving mass and information transfer, respectively. Experimental findings indicate that interfering with the feedback may substantially increase overall signaling strength, suggesting novel therapeutic targets for insulin resistance and type 2 diabetes. Because the central observations are present in other signaling networks, our results may indicate a general mechanism in hormonal control.
species: metaid_0000064
rule: metaid_0000057
species: metaid_0000022
species: metaid_0000009
parameter: metaid_0000025
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parameter: metaid_0000055
time units: time
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species: metaid_0000069
is part of: BIOMD0000000356
rule: metaid_0000052
parameter: metaid_0000056
parameter: metaid_0000033
species: metaid_0000021
species: metaid_0000018
parameter: metaid_0000039
species: metaid_0000004
species: metaid_0000019
parameter: metaid_0000028
is: MODEL1107140000
parameter: metaid_0000036
rule: metaid_0000061
compartment: metaid_0000003
parameter: metaid_0000026
rule: metaid_0000062
species: metaid_0000067
species: metaid_0000014
species: metaid_0000015
area units: area
species: metaid_0000010
species: metaid_0000011
species: metaid_0000008
parameter: metaid_0000030
parameter: metaid_0000040
rule: metaid_0000041
parameter: metaid_0000034
species: metaid_0000068
rule: metaid_0000046

metaid_0000064
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: simXp
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metaid_0000016
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V1d
type: Species

metaid_0000039
is: SBO:0000009
constant: true
value: 13740.4321729991
name: kyDosR
type: Parameter

metaid_0000035
is: SBO:0000009
constant: true
value: 0.1131073982
name: km3
type: Parameter

metaid_0000006
in compartment: metaid_0000003
is: SBO:0000240
type: Species
constant: false
initial amount: 0.0
is version of: P06213
name: IRp
initial concentration: NaN
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has only substance units: false
is version of: C00562

metaid_0000014
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
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name: V1b
type: Species

metaid_0000069
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: measdosR
type: Species

metaid_0000040
is: SBO:0000196
constant: true
value: 100.0
name: ins
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metaid_0000010
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constant: false
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initial amount: 0.0
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is: SBO:0000240
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metaid_0000030
is: SBO:0000009
constant: true
value: 3.6327773442
name: k1r
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metaid_0000020
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V2
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metaid_0000024
is: SBO:0000009
constant: true
value: 0.3892881852
name: k1a
type: Parameter

metaid_0000038
is: SBO:0000009
constant: true
value: 16760.1203140926
name: kyanna
type: Parameter

metaid_0000065
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: intamount
type: Species

metaid_0000034
is: SBO:0000009
constant: true
value: 1.6286590231
name: k3
type: Parameter

metaid_0000017
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V1e
type: Species

metaid_0000007
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is: SBO:0000240
boundary condition: true
has only substance units: false
is version of: C00562
is version of: P06213
initial concentration: NaN
type: Species
name: IRip
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metaid_0000003
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartemnt 1
type: Compartment

metaid_0000055
is: SBO:0000009
constant: true
value: 0.3635167928
name: k1c
type: Parameter

W3 CDTF: Thu Aug 09 17:41:42 BST 2012

metaid_0000056
is: SBO:0000009
constant: true
value: 1580.6782649401
name: k1d
type: Parameter

metaid_0000013
constant: false
boundary condition: true
has only substance units: false
initial concentration: 389.41271264
initial amount: NaN
in compartment: metaid_0000003
name: V1a
type: Species

metaid_0000027
is: SBO:0000009
constant: true
value: 4.38334E-5
name: k1e
type: Parameter

metaid_0000028
is: SBO:0000009
constant: true
value: 20.0726035037
name: k1f
type: Parameter

metaid_0000023
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: Vm3
type: Species

metaid_0000018
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V1g
type: Species

metaid_0000033
is: SBO:0000009
constant: true
value: 32.5942371891
name: km2
type: Parameter

metaid_0000008
initial amount: 0.0
in compartment: metaid_0000003
is version of: P06213
name: IRi
initial concentration: NaN
boundary condition: true
has only substance units: false
type: Species
is: SBO:0000240
constant: false

metaid_0000037
is: SBO:0000009
constant: true
value: 8936.219557405
name: ky2
type: Parameter

metaid_0000066
is: SBO:0000196
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: metaid_0000003
name: measIRp
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metaid_0000004
is: SBO:0000244
initial amount: 10.0
name: IR
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is: P06213
type: Species
boundary condition: true
has only substance units: false
constant: false
in compartment: metaid_0000003

metaid_0000026
is: SBO:0000009
constant: true
value: 0.02000224505
name: k1b
type: Parameter

metaid_0000012
boundary condition: true
has only substance units: false
type: Species
constant: false
name: Xp
is: CHEBI:36080
initial amount: 0.0
in compartment: metaid_0000003
is: SBO:0000240
is: FMA:74531
initial concentration: NaN

metaid_0000022
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: V3
type: Species

metaid_0000029
is: SBO:0000009
constant: true
value: 286.6994648072
name: k1g
type: Parameter

metaid_0000019
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: v1r
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metaid_0000032
is: SBO:0000009
constant: true
value: 0.036381619
name: k22
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metaid_0000067
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000003
name: measdoublestep
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metaid_0000009
initial amount: NaN
is version of: P35568
is: SBO:0000240
initial concentration: 10.0
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boundary condition: true
has only substance units: false
type: Species
constant: false
name: IRS

metaid_0000036
is: SBO:0000009
constant: true
value: 152.9631668536
name: ky1
type: Parameter

metaid_0000005
name: IRins
initial amount: 0.0
in compartment: metaid_0000003
type: Species
is: SBO:0000240
has part: P06213
has part: P01308
boundary condition: true
has only substance units: false
constant: false
initial concentration: NaN

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

W3 CDTF: Thu Jul 14 15:54:55 BST 2011