- Author:
- Soroush <ssaf006@aucklanduni.ac.nz>
- Date:
- 2017-03-22 18:43:24+13:00
- Desc:
- fixing the parameters
- Permanent Source URI:
- https://models.cellml.org/workspace/483/rawfile/7557355d7165ae1141ab6f2ab57ad7e8b2e20dcd/2-AdiposeTissueLevel.cellml
<?xml version='1.0'?>
<model name="main2" xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cellml="http://www.cellml.org/cellml/1.1#" xmlns:xlink="http://www.w3.org/1999/xlink">
<!-- in: r1x2,r11x2,r1x22,r1x22d,r11x22,rendP,rPbasal
out: X_P,vglucoseuptake-->
<import xlink:href="Units.cellml">
<units name="l_per_kg" units_ref="l_per_kg"/>
<units name="per_s" units_ref="per_s"/>
<units name="s_kg_per_pmol" units_ref="s_kg_per_pmol"/>
<units name="mg" units_ref="mg"/>
<units name="per_mg" units_ref="per_mg"/>
<units name="mg_per_kg_s" units_ref="mg_per_kg_s"/>
<units name="mg_l_per_kg_s_pmol" units_ref="mg_l_per_kg_s_pmol"/>
<units name="mg_per_s_pmol" units_ref="mg_per_s_pmol"/>
<units name="mg_per_kg" units_ref="mg_per_kg"/>
<units name="pmol_l_per_kg_mg" units_ref="pmol_l_per_kg_mg"/>
<units name="pmol_l_per_kg_mg_s" units_ref="pmol_l_per_kg_mg_s"/>
<units name="pmol_per_kg" units_ref="pmol_per_kg"/>
<units name="pmol_per_l" units_ref="pmol_per_l"/>
<units name="mg_per_l" units_ref="mg_per_l"/>
<units name="pmol_per_kg_s" units_ref="pmol_per_kg_s"/>
<units name="l_per_mol_s" units_ref="l_per_mol_s"/>
<units name="mol_per_l" units_ref="mol_per_l"/>
</import>
<import xlink:href="Parameters.cellml">
<component component_ref="param2" name="param"/>
</import>
<component name="environment">
<variable name="time" public_interface="out" units="second"/>
</component>
<component name="state">
<variable name="t" public_interface="in" units="second"/>
<!-- Parameters-->
<variable name="k21" public_interface="in" units="per_s"/>
<variable name="k22" public_interface="in" units="per_s"/>
<variable name="k23" public_interface="in" units="per_s"/>
<variable name="k24" public_interface="in" units="per_s"/>
<variable name="k2b" public_interface="in" units="per_s"/>
<variable name="k3f" public_interface="in" units="per_s"/>
<variable name="k3b" public_interface="in" units="per_s"/>
<variable name="k4f" public_interface="in" units="per_s"/>
<variable name="k4b" public_interface="in" units="per_s"/>
<variable name="k5f" public_interface="in" units="per_s"/>
<variable name="k5b" public_interface="in" units="per_s"/>
<variable name="k6f" public_interface="in" units="per_s"/>
<variable name="k6b" public_interface="in" units="per_s"/>
<variable name="k7f" public_interface="in" units="per_s"/>
<variable name="k7b" public_interface="in" units="per_s"/>
<variable name="k8f" public_interface="in" units="per_s"/>
<variable name="k8b" public_interface="in" units="per_s"/>
<variable name="k91" public_interface="in" units="per_s"/>
<variable name="k9b" public_interface="in" units="per_s"/>
<variable name="k92" public_interface="in" units="per_s"/>
<variable name="k5BasicWb" public_interface="in" units="per_s"/>
<variable name="k_glut1" public_interface="in" units="mg_per_kg_s"/>
<variable name="k_glut4" public_interface="in" units="mg_per_kg_s"/>
<variable name="KmG1" public_interface="in" units="mg_per_kg"/>
<variable name="KmG4" public_interface="in" units="mg_per_kg"/>
<variable name="kbf" public_interface="in" units="mg_l_per_kg_s_pmol"/>
<!-- State variables-->
<!-- IRS1: Insulin receptor substrate-1
IRS1iP: phosphorylated (active) form of IRS1
X: downstream intermediate which dephosphorylates IR in its active form
X_P: active form of X
PI3K: phosphatidylinositol 3-kinases
PI3K_: active form of PI3K
PDK1: 3-phosphoinositide dependent protein kinase-1 active
PDK1_: active form of PDK1
PKC: protein kinase C
PKC_P: phosphorylated (active) form of PKC
PKB: protein kinase B
PKB_P: phosphorylated (active) form of PKB
mTOR: mammalian target of rapamycin
mTOR_: active form of mTOR
GLUT4_C: glucose transporter 4 in vesicles in the cytosol
GLUT4_M: glucose transporter 4 in the plasma membrane ready to take up glucose-->
<variable initial_value="9.99982" name="IRS1" public_interface="out" units="dimensionless"/>
<variable initial_value="0.00018" name="IRS1iP" public_interface="out" units="dimensionless"/>
<variable initial_value="9.92463" name="X" units="dimensionless"/>
<variable initial_value="0.07537" name="X_P" public_interface="out" units="dimensionless"/>
<variable initial_value="9.97578" name="PI3K" units="dimensionless"/>
<variable initial_value="0.02422" name="PI3K_" units="dimensionless"/>
<variable initial_value="8.65877" name="PDK1" units="dimensionless"/>
<variable initial_value="1.34123" name="PDK1_" units="dimensionless"/>
<variable initial_value="3.60284e-5" name="PKC" units="dimensionless"/>
<variable initial_value="9.99996" name="PKC_P" units="dimensionless"/>
<variable initial_value="9.90193" name="PKB" units="dimensionless"/>
<variable initial_value="0.09807" name="PKB_P" units="dimensionless"/>
<variable initial_value="0.02019" name="mTOR" units="dimensionless"/>
<variable initial_value="9.97981" name="mTOR_" units="dimensionless"/>
<variable initial_value="9.99317" name="GLUT4_C" units="dimensionless"/>
<variable initial_value="0.00683" name="GLUT4_M" units="dimensionless"/>
<variable name="v2f" units="per_s"/>
<variable name="v2b" units="per_s"/>
<variable name="v3f" units="per_s"/>
<variable name="v3b" units="per_s"/>
<variable name="v4f" units="per_s"/>
<variable name="v4b" units="per_s"/>
<variable name="v5f" units="per_s"/>
<variable name="v5b" units="per_s"/>
<variable name="v6f" units="per_s"/>
<variable name="v6b" units="per_s"/>
<variable name="v7f" units="per_s"/>
<variable name="v7b" units="per_s"/>
<variable name="v8f" units="per_s"/>
<variable name="v8b" units="per_s"/>
<variable name="v9f" units="per_s"/>
<variable name="v9b" units="per_s"/>
<variable name="rendP" public_interface="in" units="dimensionless"/>
<variable name="r1x2" public_interface="in" units="dimensionless"/>
<variable name="r11x2" public_interface="in" units="dimensionless"/>
<variable name="r1x22" public_interface="in" units="dimensionless"/>
<variable name="r1x22d" public_interface="in" units="dimensionless"/>
<variable name="r11x22" public_interface="in" units="dimensionless"/>
<variable name="rPbasal" public_interface="in" units="dimensionless"/>
<variable name="INS" public_interface="in" units="pmol_per_l"/>
<variable name="G_t" public_interface="in" units="mg_per_kg"/>
<variable name="vglucoseuptake" public_interface="out" units="mg_per_kg_s"/>
<!-- Conservation laws-->
<!-- IRS1 and X dynamics-->
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>IRS1</ci>
</apply>
<apply>
<minus/>
<ci>v2b</ci>
<ci>v2f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>IRS1iP</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v2b</ci>
</apply>
<ci>v2f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>X</ci>
</apply>
<apply>
<minus/>
<ci>v3b</ci>
<ci>v3f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>X_P</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v3b</ci>
</apply>
<ci>v3f</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v2f</ci>
<apply>
<times/>
<ci>k21</ci>
<ci>IRS1</ci>
<apply>
<plus/>
<ci>r1x2</ci>
<ci>r11x2</ci>
<ci>r1x22</ci>
<ci>r1x22d</ci>
<ci>r11x22</ci>
<ci>rPbasal</ci>
<apply>
<times/>
<ci>k22</ci>
<ci>rendP</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>k23</ci>
<ci>PKC_P</ci>
</apply>
<apply>
<times/>
<ci>k24</ci>
<ci>mTOR</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>v2b</ci>
<apply>
<times/>
<ci>k2b</ci>
<ci>IRS1iP</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v3f</ci>
<apply>
<times/>
<ci>k3f</ci>
<ci>X</ci>
<ci>IRS1iP</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v3b</ci>
<apply>
<times/>
<ci>k3b</ci>
<ci>X_P</ci>
</apply>
</apply>
<!-- PI3K and PDK1 dynamics-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PI3K</ci>
</apply>
<apply>
<minus/>
<ci>v4b</ci>
<ci>v4f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PI3K_</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v4b</ci>
</apply>
<ci>v4f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PDK1</ci>
</apply>
<apply>
<minus/>
<ci>v5b</ci>
<ci>v5f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PDK1_</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v5b</ci>
</apply>
<ci>v5f</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v4f</ci>
<apply>
<times/>
<ci>k4f</ci>
<ci>PI3K</ci>
<ci>IRS1iP</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v4b</ci>
<apply>
<times/>
<ci>k4b</ci>
<ci>PI3K_</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v5f</ci>
<apply>
<times/>
<ci>k5f</ci>
<ci>PDK1</ci>
<ci>PI3K_</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v5b</ci>
<apply>
<times/>
<ci>k5b</ci>
<ci>PDK1_</ci>
</apply>
</apply>
<!-- PKC and PKB dynamics-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PKC</ci>
</apply>
<apply>
<minus/>
<ci>v6b</ci>
<ci>v6f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PKC_P</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v6b</ci>
</apply>
<ci>v6f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PKB</ci>
</apply>
<apply>
<minus/>
<ci>v7b</ci>
<ci>v7f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PKB_P</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v7b</ci>
</apply>
<ci>v7f</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v6f</ci>
<apply>
<times/>
<ci>k6f</ci>
<ci>PKC</ci>
<ci>PDK1_</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v6b</ci>
<apply>
<times/>
<ci>k6b</ci>
<ci>PKC_P</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v7f</ci>
<apply>
<times/>
<ci>k7f</ci>
<ci>PKB</ci>
<ci>PDK1_</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v7b</ci>
<apply>
<times/>
<ci>k7b</ci>
<ci>PKB_P</ci>
</apply>
</apply>
<!-- mTOR and GLUT4 dynamics-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>mTOR</ci>
</apply>
<apply>
<minus/>
<ci>v8b</ci>
<ci>v8f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>mTOR_</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v8b</ci>
</apply>
<ci>v8f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>GLUT4_C</ci>
</apply>
<apply>
<minus/>
<ci>v9b</ci>
<ci>v9f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>GLUT4_M</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v9b</ci>
</apply>
<ci>v9f</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v8f</ci>
<apply>
<times/>
<ci>k8f</ci>
<ci>mTOR</ci>
<ci>PKB_P</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v8b</ci>
<apply>
<times/>
<ci>k8b</ci>
<ci>mTOR_</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v9f</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k91</ci>
<ci>GLUT4_C</ci>
<ci>PKC_P</ci>
</apply>
<apply>
<times/>
<ci>k92</ci>
<ci>GLUT4_C</ci>
<ci>PKB_P</ci>
</apply>
<apply>
<times/>
<ci>k5BasicWb</ci>
<ci>GLUT4_C</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>v9b</ci>
<apply>
<times/>
<ci>k9b</ci>
<ci>GLUT4_M</ci>
</apply>
</apply>
<!-- Glucose uptake dynamics-->
<apply>
<eq/>
<ci>vglucoseuptake</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>k_glut1</ci>
<ci>G_t</ci>
</apply>
<apply>
<plus/>
<ci>KmG1</ci>
<ci>G_t</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>k_glut4</ci>
<ci>GLUT4_M</ci>
<ci>G_t</ci>
</apply>
<apply>
<plus/>
<ci>KmG4</ci>
<ci>G_t</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kbf</ci>
<apply>
<plus/>
<ci>INS</ci>
<cn cellml:units="dimensionless">5</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="state" component_2="param"/>
<map_variables variable_1="k21" variable_2="k21"/>
<map_variables variable_1="k22" variable_2="k22"/>
<map_variables variable_1="k23" variable_2="k23"/>
<map_variables variable_1="k24" variable_2="k24"/>
<map_variables variable_1="k2b" variable_2="k2b"/>
<map_variables variable_1="k3f" variable_2="k3f"/>
<map_variables variable_1="k3b" variable_2="k3b"/>
<map_variables variable_1="k4f" variable_2="k4f"/>
<map_variables variable_1="k4b" variable_2="k4b"/>
<map_variables variable_1="k5f" variable_2="k5f"/>
<map_variables variable_1="k5b" variable_2="k5b"/>
<map_variables variable_1="k6f" variable_2="k6f"/>
<map_variables variable_1="k6b" variable_2="k6b"/>
<map_variables variable_1="k7f" variable_2="k7f"/>
<map_variables variable_1="k7b" variable_2="k7b"/>
<map_variables variable_1="k8f" variable_2="k8f"/>
<map_variables variable_1="k8b" variable_2="k8b"/>
<map_variables variable_1="k91" variable_2="k91"/>
<map_variables variable_1="k9b" variable_2="k9b"/>
<map_variables variable_1="k92" variable_2="k92"/>
<map_variables variable_1="k5BasicWb" variable_2="k5BasicWb"/>
<map_variables variable_1="k_glut1" variable_2="k_glut1"/>
<map_variables variable_1="k_glut4" variable_2="k_glut4"/>
<map_variables variable_1="KmG1" variable_2="KmG1"/>
<map_variables variable_1="KmG4" variable_2="KmG4"/>
<map_variables variable_1="kbf" variable_2="kbf"/>
</connection>
<connection>
<map_components component_1="environment" component_2="state"/>
<map_variables variable_1="time" variable_2="t"/>
</connection>
</model>
