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BIOMD0000000449
name: Brännmark2013 - Insulin signalling in human adipocytes (diabetic condition)
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is: MODEL1304160000
type: SBMLModel
notes: Brännmark2013 - Insulin signalling in human adipocytes (diabetic condition) The paper describes insulin signalling in human adipocytes under normal and diabetic states using mathematical models based on experimental data. This model corresponds to insulin signalling under diabetic condtion This model is described in the article: Insulin Signaling in Type 2 Diabetes: EXPERIMENTAL AND MODELING ANALYSES REVEAL MECHANISMS OF INSULIN RESISTANCE IN HUMAN ADIPOCYTES. Brännmark C, Nyman E, Fagerholm S, Bergenholm L, Ekstrand EM, Cedersund G, Strålfors P. J Biol Chem. 2013 Apr 5;288(14):9867-80. Abstract: Type 2 diabetes originates in an expanding adipose tissue that for unknown reasons becomes insulin resistant. Insulin resistance reflects impairments in insulin signaling, but mechanisms involved are unclear because current research is fragmented. We report a systems level mechanistic understanding of insulin resistance, using systems wide and internally consistent data from human adipocytes. Based on quantitative steady-state and dynamic time course data on signaling intermediaries, normally and in diabetes, we developed a dynamic mathematical model of insulin signaling. The model structure and parameters are identical in the normal and diabetic states of the model, except for three parameters that change in diabetes: (i) reduced concentration of insulin receptor, (ii) reduced concentration of insulin-regulated glucose transporter GLUT4, and (iii) changed feedback from mammalian target of rapamycin in complex with raptor (mTORC1). Modeling reveals that at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, which explains reduced sensitivity and signal strength throughout the signaling network. Model simulations with inhibition of mTORC1 are comparable with experimental data on inhibition of mTORC1 using rapamycin in human adipocytes. We demonstrate the potential of the model for identific…
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constant: true
value: 31.01
name: k1d
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#f9563b54_50d9_40e8_80c4_4adf8a354cf5
constant: false
value: 0.0
name: measuredIRp
type: Parameter

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type: Reaction
reversible: false
fast: false
name: v4c

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stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_1c5e4e2c_f319_4500_a348_559b7b1fdf55
stoichiometry: 1.0
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http://identifiers.org/biomodels.db/BIOMD0000000449#_6694ce23_de30_489e_b4d1_4b5deda1fb41
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#f49e2c02_201f_4970_8f17_3b42a6d67116
constant: true
value: 2.137
name: n6
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_25eba3cb_5c70_4539_8269_3cce2d44a8c2
constant: false
boundary condition: false
has only substance units: false
initial concentration: 78.0219322115859
initial amount: NaN
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constant: false
value: 0.0
name: measuredmTORC2a
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#e338fcc2_99b6_4e86_b4e5_0337f3abc33d
reversible: false
type: Reaction
fast: false
name: v4e

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stoichiometry: 1.0
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http://identifiers.org/biomodels.db/BIOMD0000000449#_11ee4ce2_1d63_4796_b8be_47faddf8ade2
stoichiometry: 1.0
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http://identifiers.org/biomodels.db/BIOMD0000000449#e251119e_38cd_4dac_a9e4_1a17e431174c
stoichiometry: 1.0
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fast: false
reversible: false
name: v1r
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stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#fd60b0d6_3084_4084_8cb4_8e536690ebdc
stoichiometry: 1.0
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http://identifiers.org/biomodels.db/BIOMD0000000449#_0aec90ba_4031_446e_8129_c0d022eb6887
stoichiometry: 1.0
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http://identifiers.org/biomodels.db/BIOMD0000000449#_5e672459_897f_49b4_99d5_b4655dd68b53
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_9bbefb9e_cd73_447e_a6ef_604ee58ea747
constant: true
value: 0.001377
name: k3a
type: Parameter

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.170313993390069
initial amount: NaN
name: S6Kp
type: Species

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fast: false
reversible: false
name: v4b
type: Reaction

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fast: false
reversible: false
name: v1g
type: Reaction

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 96.927052256569
initial amount: NaN
name: mTORC1
type: Species

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stoichiometry: 1.0
type: SpeciesReference

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fast: false
reversible: false
name: v4h
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stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_708e532d_3f73_4f8d_a2a9_57b8370df81e
stoichiometry: 1.0
type: SpeciesReference

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.011815001204792
initial amount: NaN
name: IRip
type: Species

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constant: true
value: 0.03683
name: k1basal
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#ae4a7237_8ac3_41e1_8062_0ea0bf12b5c1
constant: true
value: 1.842
name: k5a1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_442610a7_4172_42f4_a1e8_ea79d2358cba
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_899d9dbf_d454_44b4_9791_0bad96ac3408
fast: false
reversible: false
name: v9b2
type: Reaction

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 45.4119141649757
initial amount: NaN
name: GLUT4
type: Species

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.31221500588088E-4
initial amount: NaN
name: IRp
type: Species

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constant: true
value: 0.09876
name: k3b
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_6163d3d0_1196_477f_9980_ae350f236ec6
constant: true
value: 3424.0
name: k2b
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#f16895f4_a1af_4936_92fd_649ec2f7a8be
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_6bbae286_846e_431d_b0d4_05120993cef7
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.6963389945784
initial amount: NaN
name: PKB473p
type: Species

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constant: true
value: 30.54
name: km6
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_255e6ba2_3883_4305_9f16_1555e3b1286b
constant: true
value: 5.202
name: scaleIR
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_0323eccb_04bf_4b70_a53e_c3a8abd13f23
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#dbbf832c_a460_4c5e_9105_5fbeb69aae48
stoichiometry: 1.0
type: SpeciesReference

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constant: true
value: 143.6
name: k4f
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_79aac60b_7b30_4570_b0c0_e4fec8790628
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_9dc8477f_43a7_41e7_927c_8d27147c8ee3
constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.8296860066098
initial amount: NaN
name: S6K
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000449#_139496d4_1990_4a17_af10_9b0356a8175d
constant: true
value: 1944.0
name: k1g
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#cb445116_cb42_4c11_8e16_88df21a5a15c
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#cec1d269_592b_45fb_8ffd_f299dade4489
constant: false
value: 0.0
name: measuredIRS1307
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_10b6893e_cfda_4878_8c2e_55e9369c53eb
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.061992532897245
initial amount: NaN
name: PKB308p473p
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000449#_510b5cbc_6152_4b40_90b8_3a85c79a0fec
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_887b0bf7_b516_4f30_89b3_f6d26a91a308
constant: true
value: 0.04441
name: k9b1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#e773ae6b_9412_4b7e_bb25_fb6e71df15c1
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_99847641_8a89_4014_a6e2_df20e64d6cb0
name: v4a
type: Reaction
fast: false
reversible: false

http://identifiers.org/biomodels.db/BIOMD0000000449#_8ad965f7_7e51_4d2a_86f1_6e26af469e91
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_69a0aae2_0a57_491f_914a_eb77c7bcfb63
constant: true
value: 0.1149
name: scaleS6
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_57669088_325e_414d_8967_b9f651f295e5
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_47e88285_f8ac_4c5f_b200_941f64b12213
constant: false
value: 0.0
name: measuredS6Kp
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_769274b7_0fa4_4975_83fd_c032c4da576c
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_53ef39a0_1efc_44be_b32f_82bfbfc276b1
constant: false
value: 0.0
name: measuredIRint
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_36456197_988d_4747_9b24_2213486e4c35
fast: false
reversible: false
name: v5b
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000449#_061732c3_dfe9_4c19_91c8_234aecc3bd27
constant: true
value: 0.15
name: diabetes
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#b9c11e92_4134_416d_833b_71a6af5f2e92
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_5e2c2d3f_cc8b_43ae_bcb3_bb9d558b3c7b
constant: true
value: 0.5471
name: k1r
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_89811454_ee8a_4a24_835c_3c5775dd007e
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#cddeecc2_691f_46bb_9ffb_49e8bc2da651
constant: true
value: 0.026656
name: scaleAS160
type: Parameter

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stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#_2cfdaa89_9276_46ce_9204_fc04d0608cb1
fast: false
reversible: false
name: v6b1
type: Reaction

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constant: true
value: 5873.0
name: km9
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_4f689140_6b52_4f2a_bdf7_1dbf4eebe100
constant: true
value: 0.5361
name: k4h
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#_1cdc7d42_c572_4a29_873f_281d7dabe3f6
fast: false
reversible: false
name: v2f
type: Reaction

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constant: true
value: 36.93
name: k6f2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000449#ba27544f_b7a7_4cf4_92a2_175d03bd5869
fast: false
reversible: false
name: v1basal
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0527894351383809
initial amount: NaN
name: IRi
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constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.5272377217019E-4
initial amount: NaN
name: IRS1p
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stoichiometry: 1.0
type: SpeciesReference

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.9986712896423
initial amount: NaN
name: X
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type: Reaction
reversible: false
name: v3a
fast: false

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stoichiometry: 1.0
type: SpeciesReference

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.00132871035763352
initial amount: NaN
name: Xp
type: Species

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fast: false
type: Reaction
name: v5a
reversible: false

http://identifiers.org/biomodels.db/BIOMD0000000449#_2e714678_1b06_476a_b571_0b11736a6371
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000449#c6dc0272_8e22_417a_83d8_fc559fe22977
constant: true
value: 2.913
name: k2f
type: Parameter

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.07294774343092
initial amount: NaN
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constant: false
value: 0.0
name: glucoseuptake
type: Parameter

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fast: false
reversible: false
name: v5d
type: Reaction

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stoichiometry: 1.0
type: SpeciesReference

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name: v6f1
fast: false
reversible: false
type: Reaction

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fast: false
reversible: false
name: v2d
type: Reaction

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stoichiometry: 1.0
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