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BIOMD0000000137 - Sedaghat2002_InsulinSignalling_noFeedback

 

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Reference Publication
Publication ID: 12376338
Sedaghat AR, Sherman A, Quon MJ.
A mathematical model of metabolic insulin signaling pathways.
Am. J. Physiol. Endocrinol. Metab. 2002 Nov; 283(5): E1084-101
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.  [more]
Model
Original Model: BIOMD0000000137.xml.origin
Submitter: Harish Dharuri
Submission ID: MODEL6526728774
Submission Date: 08 Aug 2007 07:34:07 UTC
Last Modification Date: 05 Jun 2013 10:40:57 UTC
Creation Date: 06 Aug 2007 15:09:19 UTC
Encoders:  Harish Dharuri
set #1
bqbiol:isPartOf KEGG Pathway hsa04910
Gene Ontology insulin receptor signaling pathway
bqbiol:occursIn Taxonomy Homo sapiens
Notes

Model reproduces the various plots in Figure 6 and 7 of the paper. It was successfully tested on MathSBML.


To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.


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, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 12376338 Submission Date: 08 Aug 2007 07:34:07 UTC Last Modification Date: 05 Jun 2013 10:40:57 UTC Creation Date: 06 Aug 2007 15:09:19 UTC
Mathematical expressions
Reactions
Insulin binding Receptor Autophosphorylation Insulin Binding Receptor dephosphorylation
Receptor endocytosis Receptor transport Receptor transport Receptor synthesis
Receptor degradation Intracellular receptor dephosphorylation Intracellular receptor dephosphorylation IRS1 activation
IRS1-PI3K complex formation PI 3,4,5 P3 generation PI 3,4,5P3 generation Akt activation
PKC activation GLUT4 synthesis GLUT4 degradation GLUT4 translocation
Rules
Assignment Rule (variable: k9) Assignment Rule (variable: k11) Assignment Rule (variable: k12) Assignment Rule (variable: Effect)
Assignment Rule (variable: k13prime) Assignment Rule (variable: x4x5)    
Events
event_0000001 event_0000002 event_0000003  
Physical entities
Compartments Species
CellSurface Insulin Unbound Insulin Receptor Unphosphorylated once bound receptor
Phosphorylated once bound receptor Phosphorylated twice bound receptor Cell surface GLUT4
Intracellular Unbound unphosphorylated intracellular receptor Phosphorylated twice bound intracellular receptor Phosphorylated once bound intracellular receptor
Unphosphorylated IRS1 Phosphorylated IRS1 PI3 Kinase
IRS1- PI3 Kinase Complex PI3,4,5P3 PI4,5P2
PI3,4P2 Unactivated Akt Activated Akt
Unactivated PKC Activated PKC Intracellular GLUT4
     
Global parameters
k1 kminus1 k2 kminus2
k3 kminus3 k4 kminus4
k4prime kminus4prime k5 kminus5
k6 k7 kminus7 k8
kminus8 k9 k9_stimulated k9_basal
kminus9 k10 kminus10 k11
kminus11 k12 kminus12 k13
kminus13 k13prime k14 kminus14
Effect IRp SHIP PTEN
PTP APequil PI3K x4x5
Reactions (20)
 
 Insulin binding [Unbound Insulin Receptor] ↔ [Unphosphorylated once bound receptor];   {Insulin}
 
 Receptor Autophosphorylation [Unphosphorylated once bound receptor] → [Phosphorylated once bound receptor];  
 
 Insulin Binding [Phosphorylated once bound receptor] ↔ [Phosphorylated twice bound receptor];   {Insulin}
 
 Receptor dephosphorylation [Phosphorylated once bound receptor] → [Unbound Insulin Receptor];  
 
 Receptor endocytosis [Unbound Insulin Receptor] ↔ [Unbound unphosphorylated intracellular receptor];  
 
 Receptor transport [Phosphorylated twice bound receptor] ↔ [Phosphorylated twice bound intracellular receptor];  
 
 Receptor transport [Phosphorylated once bound receptor] ↔ [Phosphorylated once bound intracellular receptor];  
 
 Receptor synthesis  → [Unbound unphosphorylated intracellular receptor];  
 
 Receptor degradation [Unbound unphosphorylated intracellular receptor] → ;  
 
 Intracellular receptor dephosphorylation [Phosphorylated twice bound intracellular receptor] → [Unbound unphosphorylated intracellular receptor];  
 
 Intracellular receptor dephosphorylation [Phosphorylated once bound intracellular receptor] → [Unbound unphosphorylated intracellular receptor];  
 
 IRS1 activation [Unphosphorylated IRS1] ↔ [Phosphorylated IRS1];   {Phosphorylated twice bound receptor} , {Phosphorylated once bound receptor}
 
 IRS1-PI3K complex formation [PI3 Kinase] + [Phosphorylated IRS1] ↔ [IRS1- PI3 Kinase Complex];  
 
 PI 3,4,5 P3 generation [PI4,5P2] ↔ [PI3,4,5P3];  
 
 PI 3,4,5P3 generation [PI3,4P2] ↔ [PI3,4,5P3];  
 
 Akt activation [Unactivated Akt] ↔ [Activated Akt];  
 
 PKC activation [Unactivated PKC] ↔ [Activated PKC];  
 
 GLUT4 synthesis  → [Intracellular GLUT4];  
 
 GLUT4 degradation [Intracellular GLUT4] → ;  
 
 GLUT4 translocation [Intracellular GLUT4] ↔ [Cell surface GLUT4];  
 
Rules (6)
 
 Assignment Rule (name: k9) k9 = (k9_stimulated+k9_basal)*x12/PI3K+k9_basal
 
 Assignment Rule (name: k11) k11 = 0.1*kminus11*(x13-0.31)/(3.1-0.31)
 
 Assignment Rule (name: k12) k12 = 0.1*kminus12*(x13-0.31)/(3.1-0.31)
 
 Assignment Rule (name: Effect) Effect = (0.2*x17+0.8*x19)/APequil
 
 Assignment Rule (name: k13prime) k13prime = (40/60-4/96)*kminus13*Effect
 
 Assignment Rule (name: x4x5) x4x5 = x4+x5
 
Events (3)
 
 event_0000001
Insulin = 0
 
 event_0000002
k5 = 1.67E-2
 
 event_0000003
k5 = 0.1002
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Insulin
Compartment: CellSurface
Initial concentration: 1.0E8
 
 Unbound Insulin Receptor
Compartment: CellSurface
Initial concentration: 900.0
 
 Unphosphorylated once bound receptor
Compartment: CellSurface
Initial concentration: 0.0
 
 Phosphorylated once bound receptor
Compartment: CellSurface
Initial concentration: 0.0
 
 Phosphorylated twice bound receptor
Compartment: CellSurface
Initial concentration: 0.0
 
 Cell surface GLUT4
Compartment: CellSurface
Initial concentration: 4.0
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Unbound unphosphorylated intracellular receptor
Compartment: Intracellular
Initial concentration: 100.0
 
 Phosphorylated twice bound intracellular receptor
Compartment: Intracellular
Initial concentration: 0.0
 
 Phosphorylated once bound intracellular receptor
Compartment: Intracellular
Initial concentration: 0.0
 
 Unphosphorylated IRS1
Compartment: Intracellular
Initial concentration: 1000.0
 
 Phosphorylated IRS1
Compartment: Intracellular
Initial concentration: 0.0
 
 PI3 Kinase
Compartment: Intracellular
Initial concentration: 100.0
 
 IRS1- PI3 Kinase Complex
Compartment: Intracellular
Initial concentration: 0.0
 
 PI3,4,5P3
Compartment: Intracellular
Initial concentration: 0.31
 
 PI4,5P2
Compartment: Intracellular
Initial concentration: 99.4
 
 PI3,4P2
Compartment: Intracellular
Initial concentration: 0.29
 
 Unactivated Akt
Compartment: Intracellular
Initial concentration: 100.0
 
 Activated Akt
Compartment: Intracellular
Initial concentration: 0.0
 
 Unactivated PKC
Compartment: Intracellular
Initial concentration: 100.0
 
 Activated PKC
Compartment: Intracellular
Initial concentration: 0.0
 
 Intracellular GLUT4
Compartment: Intracellular
Initial concentration: 96.0
 
Global Parameters (40)
 
   k1
Value: 6.0E-8
Constant
 
   kminus1
Value: 0.2
Constant
 
   k2
Value: 6.0E-8
Constant
 
   kminus2
Value: 20.0
Constant
 
   k3
Value: 2500.0
Constant
 
   kminus3
Value: 0.2
Constant
 
   k4
Value: 3.3333334E-4
Constant
 
   kminus4
Value: 0.0030
Constant
 
   k4prime
Value: 0.0021
Constant
 
   kminus4prime
Value: 2.1E-4
Constant
 
   k5  
 
   kminus5
Value: 1.67E-18
Constant
 
   k6
Value: 0.461
Constant
 
   k7
Value: 4.16
Constant
 
   kminus7
Value: 1.396
Constant
 
   k8
Value: 7.06E-4
Constant
 
   kminus8
Value: 10.0
Constant
 
   k9  
 
   k9_stimulated
Value: 1.39
Constant
 
   k9_basal
Value: 0.13145
Constant
 
   kminus9
Value: 42.15
Constant
 
   k10
Value: 2.961
Constant
 
   kminus10
Value: 2.77
Constant
 
   k11  
 
   kminus11
Value: 6.9315
Constant
 
   k12  
 
   kminus12
Value: 6.9315
Constant
 
   k13
Value: 0.00696
Constant
 
   kminus13
Value: 0.167
Constant
 
   k13prime  
 
   k14
Value: 0.11088
Constant
 
   kminus14
Value: 0.001155
Constant
 
   Effect  
 
   IRp
Value: 897.0
Constant
 
   SHIP
Value: 1.0
Constant
 
   PTEN
Value: 1.0
Constant
 
   PTP
Value: 1.0
Constant
 
   APequil
Value: 9.09091
Constant
 
   PI3K
Value: 5.0
Constant
 
   x4x5  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000137

Curator's comment: (updated: 07 Aug 2007 23:54:28 BST)

The above plot reproduces the time profile of various species as depicted in Figure 6 of the paper. Simulation result obtained from MathSBML.

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