Location: Diabetes @ 29dc5b30e1d8 / Original / 2-AdiposeTissueLevel.cellml

Author:
Soroush Safaei <ssaf006@aucklanduni.ac.nz>
Date:
2018-06-04 00:21:40+12:00
Desc:
adding minute units
Permanent Source URI:
https://models.physiomeproject.org/workspace/483/rawfile/29dc5b30e1d8caa484fb61f1ca92502dcac8a02d/Original/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-min.cellml">
        <units name="minute" units_ref="minute"/>
        <units name="l_per_kg" units_ref="l_per_kg"/>
        <units name="dl_per_kg" units_ref="dl_per_kg"/>
        <units name="per_minute" units_ref="per_minute"/>
        <units name="minute_kg_per_pmol" units_ref="minute_kg_per_pmol"/>
        <units name="mg" units_ref="mg"/>
        <units name="per_mg" units_ref="per_mg"/>
        <units name="mg_per_kg_minute" units_ref="mg_per_kg_minute"/>
        <units name="mg_l_per_kg_minute_pmol" units_ref="mg_l_per_kg_minute_pmol"/>
        <units name="mg_per_minute_pmol" units_ref="mg_per_minute_pmol"/>
        <units name="mg_per_kg" units_ref="mg_per_kg"/>
        <units name="pmol_dl_per_kg_mg" units_ref="pmol_dl_per_kg_mg"/>
        <units name="pmol_dl_per_kg_mg_minute" units_ref="pmol_dl_per_kg_mg_minute"/>
        <units name="pmol_per_kg" units_ref="pmol_per_kg"/>
        <units name="pmol_per_l" units_ref="pmol_per_l"/>
        <units name="mg_per_dl" units_ref="mg_per_dl"/>
        <units name="pmol_per_kg_minute" units_ref="pmol_per_kg_minute"/>
        <units name="l_per_mol_minute" units_ref="l_per_mol_minute"/>
        <units name="mol_per_l" units_ref="mol_per_l"/>
    </import>
    <import xlink:href="Parameters-min.cellml">
        <component component_ref="param2" name="param"/>
    </import>
    <component name="environment">
        <variable name="time" public_interface="out" units="minute"/>
    </component>
    <component name="state">
        <variable name="t" public_interface="in" units="minute"/>
        <!-- Parameters-->
        <variable name="k21" public_interface="in" units="per_minute"/>
        <variable name="k22" public_interface="in" units="dimensionless"/>
        <variable name="k23" public_interface="in" units="dimensionless"/>
        <variable name="k24" public_interface="in" units="dimensionless"/>
        <variable name="k2b" public_interface="in" units="per_minute"/>
        <variable name="k3f" public_interface="in" units="per_minute"/>
        <variable name="k3b" public_interface="in" units="per_minute"/>
        <variable name="k4f" public_interface="in" units="per_minute"/>
        <variable name="k4b" public_interface="in" units="per_minute"/>
        <variable name="k5f" public_interface="in" units="per_minute"/>
        <variable name="k5b" public_interface="in" units="per_minute"/>
        <variable name="k6f" public_interface="in" units="per_minute"/>
        <variable name="k6b" public_interface="in" units="per_minute"/>
        <variable name="k7f" public_interface="in" units="per_minute"/>
        <variable name="k7b" public_interface="in" units="per_minute"/>
        <variable name="k8f" public_interface="in" units="per_minute"/>
        <variable name="k8b" public_interface="in" units="per_minute"/>
        <variable name="k91" public_interface="in" units="per_minute"/>
        <variable name="k9b" public_interface="in" units="per_minute"/>
        <variable name="k92" public_interface="in" units="per_minute"/>
        <variable name="k5BasicWb" public_interface="in" units="per_minute"/>
        <variable name="k_glut1" public_interface="in" units="mg_per_kg_minute"/>
        <variable name="k_glut4" public_interface="in" units="mg_per_kg_minute"/>
        <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_minute_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" public_interface="out" units="dimensionless"/>
        <variable initial_value="0.07537" name="X_P" public_interface="out" units="dimensionless"/>
        <variable initial_value="9.97578" name="PI3K" public_interface="out" units="dimensionless"/>
        <variable initial_value="0.02422" name="PI3K_" public_interface="out" units="dimensionless"/>
        <variable initial_value="8.65877" name="PDK1" public_interface="out" units="dimensionless"/>
        <variable initial_value="1.34123" name="PDK1_" public_interface="out" units="dimensionless"/>
        <variable initial_value="3.60284e-5" name="PKC" public_interface="out" units="dimensionless"/>
        <variable initial_value="9.99996" name="PKC_P" public_interface="out" units="dimensionless"/>
        <variable initial_value="9.90193" name="PKB" public_interface="out" units="dimensionless"/>
        <variable initial_value="0.09807" name="PKB_P" public_interface="out" units="dimensionless"/>
        <variable initial_value="0.02019" name="mTOR" public_interface="out" units="dimensionless"/>
        <variable initial_value="9.97981" name="mTOR_" public_interface="out" units="dimensionless"/>
        <variable initial_value="9.99317" name="GLUT4_C" public_interface="out" units="dimensionless"/>
        <variable initial_value="0.00683" name="GLUT4_M" public_interface="out" units="dimensionless"/>
        <variable name="v2f" public_interface="out" units="per_minute"/>
        <variable name="v2b" public_interface="out" units="per_minute"/>
        <variable name="v3f" public_interface="out" units="per_minute"/>
        <variable name="v3b" public_interface="out" units="per_minute"/>
        <variable name="v4f" public_interface="out" units="per_minute"/>
        <variable name="v4b" public_interface="out" units="per_minute"/>
        <variable name="v5f" public_interface="out" units="per_minute"/>
        <variable name="v5b" public_interface="out" units="per_minute"/>
        <variable name="v6f" public_interface="out" units="per_minute"/>
        <variable name="v6b" public_interface="out" units="per_minute"/>
        <variable name="v7f" public_interface="out" units="per_minute"/>
        <variable name="v7b" public_interface="out" units="per_minute"/>
        <variable name="v8f" public_interface="out" units="per_minute"/>
        <variable name="v8b" public_interface="out" units="per_minute"/>
        <variable name="v9f" public_interface="out" units="per_minute"/>
        <variable name="v9b" public_interface="out" units="per_minute"/>
        <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_minute"/>
        <!-- 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>