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constant: true
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BIOMD0000000448
type: SBMLModel
notes: Brännmark2013 - Insulin signalling in human adipocytes (normal 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 normal 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 identificatio…
curated: true
is: MODEL1304190000
length unit: length
name: Brännmark2013 - Insulin signalling in human adipocytes (normal condition)
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area units: area
time units: metaid_0000010

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stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_19a01c62_32c8_4713_83d2_9ef3eec25710
constant: false
value: 0.0
name: measuredAS160p
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_9fd1d212_f18c_4b73_84ea_0353a1ace236
fast: false
reversible: false
name: v2basal
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_918be03d_3fe4_43bb_b767_64d87df91d3d
constant: true
value: 3.227
name: k2a
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_87c5396d_c089_482f_ace4_187a96c62d30
reversible: false
name: v4e
type: Reaction
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000448#d92c36da_971f_4c51_a7a5_5730be73b609
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.152185153840861
initial amount: NaN
name: mTORC2a
type: Species

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constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.8737104842408
initial amount: NaN
name: IR
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_77e41c76_6493_4746_9b02_ad66744a37dc
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_43019160_3ca8_45ad_83c7_c1df78ced8e5
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#ea6e2500_8c3b_46c7_8b13_238dac6f3d73
constant: true
value: 1.06
name: k5d
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#f843a2e5_981e_4c83_9d18_ef5dba5dd908
fast: false
reversible: false
name: v6b1
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_62cc5ac6_7bd5_4961_97b0_6aefb190d401
constant: true
value: 0.08575
name: k5c
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_429a8c3b_9c42_4d39_a51c_3997591fe383
constant: false
boundary condition: false
has only substance units: false
initial concentration: 92.7596420796038
initial amount: NaN
name: S6
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#dfc419da_8d55_42ce_98b2_355e686aeba8
constant: true
value: 0.03683
name: k1basal
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#b2d0d98d_601e_4f15_bb43_3235107b0e45
constant: true
value: 34.8
name: k4b
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_3b5910a5_4487_4a6a_9263_6a9ddd3b8e71
constant: false
boundary condition: false
has only substance units: false
initial concentration: 16.7041510257561
initial amount: NaN
name: IRS1307
type: Species

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fast: false
reversible: false
name: v2g
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_0d316927_1e35_4865_ab84_e3623033d42a
constant: true
value: 3.329
name: k9f2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_85787b4e_8272_49b1_b820_a959f3ec7486
constant: true
value: 0.5471
name: k1r
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_6bb09aa8_9bb4_433a_afcc_13136603a1b1
fast: false
reversible: false
name: v9b1
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_9b4da00d_3492_4f29_b873_27e967569698
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#c2b66e2e_0962_49a1_a38c_e8119b2d5cc3
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_716a7f25_0b41_420b_86a7_6a0ffa77eff5
type: Reaction
name: v2c
fast: false
reversible: false

http://identifiers.org/biomodels.db/BIOMD0000000448#_07a0af4b_afb1_41fb_b659_4e6f515ffcef
fast: false
reversible: false
name: v7b
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#f9454196_f2ac_4503_90fe_54a689daa3ea
constant: true
value: 0.040513
name: scaleGLUCOSE
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_15617e7e_df85_4e11_8146_fb4abdb5607d
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#f7677274_3665_4618_8b47_633768e2d3f2
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_8f815f09_e6cf_4e12_a75e_4af321b70200
constant: true
value: 2.65
name: km5
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_22d20577_cf4b_40ab_8abb_0ec6a9b33041
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_2e7d8feb_916d_48c8_a8e1_c2aaea9b200e
fast: false
reversible: false
name: v1c
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_7891af92_dacb_4191_89e8_b20d07a54079
constant: true
value: 31.0
name: k9b2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_87708f27_87cc_4ca6_a617_d6f8c7bb396b
constant: true
size: 1.0
spatial dimensions: 3.0
name: cellvolume
type: Compartment

http://identifiers.org/biomodels.db/BIOMD0000000448#_4397647d_6844_46ef_a4ef_f361b1d923a3
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.00186253217635894
initial amount: NaN
name: IRp
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_2fa27184_00c4_496f_bc8f_d850b09c06d6
constant: true
value: 0.058663
name: scaleIRS1307
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_87160677_16a1_4c41_84a1_1667007e0cd2
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#d31f533d_190d_474d_99d1_450eda3689ac
constant: true
value: 5759.0
name: k2c
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_64c102e1_b359_4b16_a84f_9a661fe2595e
constant: true
value: 2.652
name: k6f1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#fe7f252a_5a11_4a9a_9b8e_88589c5a3fc6
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_49831507_2110_42dd_9850_c6a183b900e0
constant: true
value: 0.8768
name: k1c
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_13a2f168_930c_448f_a6f0_d196f7f7c4d6
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_2ba1fbac_d720_405f_baef_2ae0f68546db
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_51d506d6_afc1_41b8_9692_6badba583b39
type: Reaction
reversible: false
name: v7f
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000448#fbd6283a_aea9_4424_ad9f_114b951a2165
constant: false
boundary condition: false
has only substance units: false
initial concentration: 82.9671997523599
initial amount: NaN
name: IRS1
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#beb42d69_45a9_4dd9_8228_6d87a1ea7fa1
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_214623ae_c45d_4425_9af9_41d6b478d38f
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#b891d951_32b4_4b98_af30_c2f490404c23
constant: true
value: 2.137
name: n6
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_14bcec32_f0a4_4f32_b871_882b9572101b
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#ee7df8b0_de0c_4426_9a7e_c932494aff71
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.105583925473107
initial amount: NaN
name: IRi
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_08d40d28_bfe1_4d09_8278_3dbd18a2d968
type: Reaction
name: v4a
reversible: false
fast: false

http://identifiers.org/biomodels.db/BIOMD0000000448#b150af0f_036b_434a_b356_5488a511b726
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_20d3b82e_6cd5_4663_83bb_6e1e0cbadc72
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#fb119d48_e3c0_4453_8efe_39b50af9cf56
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_4991d3ac_8265_420d_b20c_264eec2d65f5
constant: true
value: 50.98
name: k7f
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#b318b74e_8217_4862_9ad0_ced31e7492da
constant: true
value: 4.456
name: k4c
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#c44c75a5_5bb7_45e7_b04f_44906bb0b230
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#c76d9b4c_4df7_4c51_94e7_705476535691
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_1b496d0c_adf2_4b46_9639_d41074fa331a
constant: true
value: 0.6331
name: k1a
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_57faccc1_372f_4548_8094_6e397eb1d865
constant: true
value: 0.05506
name: k5a2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_216fa1fa_dc2c_4898_9273_752fac770753
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_42533d88_e512_42da_9e82_9a5c0c907c5c
constant: true
value: 36.93
name: k6f2
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_0de862c9_3784_4e40_9b5a_52e080768f27
constant: false
value: 0.0
name: glucoseuptake
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#fab4cbc9_39d4_4017_8854_f29d3192a13c
fast: false
reversible: false
name: v1g
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_5330e394_9135_4d5b_b2cf_c5f16c474f1a
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#f8096a5d_d0f0_4aed_b8fb_1179ede8cf68
constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.2731987219547
initial amount: NaN
name: S6K
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_2d810b51_0884_4263_b40d_29238be41cc7
constant: false
boundary condition: false
has only substance units: false
initial concentration: 16.8171941560617
initial amount: NaN
name: PKB473p
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_8364bc90_b3a7_4495_a64a_830b5dd73858
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#c2b16012_5671_4bf2_9441_f511ff945819
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#c0fade3a_5441_4e81_9c41_97c98fb59afd
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#a6e9999b_f58a_4568_a8dd_ccf53c7b71e8
constant: false
boundary condition: false
has only substance units: false
initial concentration: 13.2964849666951
initial amount: NaN
name: PKB308p
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_11fc62d3_280b_414c_aea5_70fe3680d7b8
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#b6c10095_a798_41da_8dce_f3ccfe3e5725
constant: true
value: 0.74654
name: scaleS6K
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_8a2e1518_6c65_46ce_899f_c60e63d6d0db
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#eee68ec6_cf94_4806_83a8_ffed1575acb5
constant: true
value: 0.1298
name: k9f1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_4b04d45e_83fe_4488_b135_0c235d4fec5a
fast: false
reversible: false
name: v2b
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_84932f46_0a97_4661_9b6e_c768c8451239
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_3ec91c4f_57d4_4d18_b77a_940fef3be98d
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.70566051030056
initial amount: NaN
name: PKB308p473p
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#_7d3d506e_a5ab_4408_ab60_7c64f175b9cc
fast: false
reversible: false
name: v5d
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_2785b630_62bf_4893_8a62_ee1127995ad7
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#ae1b70d3_a26d_45e1_bce6_fd1adc4a3750
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_03048f15_33b6_4bea_a529_296a8407851e
constant: true
value: 1.842
name: k5a1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#_1a6aad23_ade1_4f47_bce5_cc1490c60e65
constant: true
value: 7042.0
name: glut1
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#bf89c551_3096_4754_9c38_d846c7b3b36c
fast: false
reversible: false
type: Reaction
name: v9f1

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fast: false
reversible: false
name: v5b
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#_72f626c5_741a_4d23_8478_660085032c78
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#fa6f8168_4322_4640_a03c_05f05d283fb0
stoichiometry: 1.0
type: SpeciesReference

http://identifiers.org/biomodels.db/BIOMD0000000448#_48c696eb_7b9e_4307_99a4_7a61ba1b2da3
constant: false
value: 0.0
name: measuredIRS1307
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#ff1b2daf_6960_4e57_b2f6_c66cd625ad46
fast: false
reversible: false
name: v4b
type: Reaction

http://identifiers.org/biomodels.db/BIOMD0000000448#d271d689_fa78_4c17_8321_ad2a46463ace
constant: false
boundary condition: false
has only substance units: false
initial concentration: 13.4997527759726
initial amount: NaN
name: mTORC1a
type: Species

http://identifiers.org/biomodels.db/BIOMD0000000448#f664b43e_856f_435d_937c_d503a52801b9
constant: true
value: 724.2
name: k8
type: Parameter

http://identifiers.org/biomodels.db/BIOMD0000000448#e4bca10f_fdac_45eb_a71e_5373e14a7aee
stoichiometry: 1.0
type: SpeciesReference