- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-07-09 07:29:55+12:00
- Desc:
- committing version01 of sedaghat_sherman_quon_2002
- Permanent Source URI:
- https://models.cellml.org/workspace/sedaghat_sherman_quon_2002/rawfile/5b844c50259a0b9ab72fb695413fe0d4ded597bb/sedaghat_sherman_quon_2002.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE :sedaghat_model_2002.xml
CREATED : 4th November 2002
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Sedaghat, Sherman and Quon's 2002 mathematical model of metabolic insulin signaling pathways.
CHANGES:
09/04/2003 - AAC - Added publication date information.
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="sedaghat_sherman_quon_2002_version01" name="sedaghat_sherman_quon_2002_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Mathematical Model of Metabolic Insulin Signalling Pathways</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Insulin is a peptide hormone that influences metabolism by promoting glucose uptake into tissues. Insulin-stimulated glucose transport involves the translocation of glucose transporters (GLUT4) from an intracellular location to the plasma membrane (see <xref linkend="fig_reaction_diagram"/> below). The identities of many of the intermediate components of the insulin signal transduction pathway have been elucidated. On binding insulin, the surface insulin receptor undergoes autophosphorylation and displays enhanced tyrosine kinase activity. Subsequently, downstream intracellular substances such as the insulin receptor substrate-1 (IRS-1) are phosphorylated, creating binding sites for SH2 containing proteins such as phosphatidylinositide 3-kinase (PI3K). This enzyme then catalyses the formation of phosphoinositol lipds such as PI(3,4,5)P<subscript>3</subscript>, which in turn activate 3-phosphoinositide-dependent protein kinase (PDK)-1. This then phosphorylates and activates other kinases such as protein kinase C (PKC) and Akt that mediate translocation of GLUT4. The identities of the elements linking PKC and Akt with GLUT4 translocation are as yet unknown, therefore the mechanisms underlying the control of insulin metabolism are not yet completely understood.
</para>
<para>
Complete understanding is also hindered by the complexity of signalling pathways. Many substrates are shared components of several pathways, and feedback and other interactions link individual pathways into complex signalling networks. Alfred Gilman has founded <ulink url="http://www.cellularsignaling.org/">The Alliance for Cellular Signaling</ulink> with the aim of integrating experimental data into theoretical models and increasing understanding of cell signalling. With this in mind, Ahmad R. Sedaghat, Arthur Sherman, and Michael J. Quon have developed a mathematical model of metabolic insulin signaling pathways. Their model has four main parts:
<itemizedlist>
<listitem>
<para>Insulin receptor binding subsystem;</para>
</listitem>
<listitem>
<para>Insulin receptor recycling subsystem;</para>
</listitem>
<listitem>
<para>Postreceptor signalling subsystem; and</para>
</listitem>
<listitem>
<para>Glut4 translocation subsystem.</para>
</listitem>
</itemizedlist>
All rate constants and model parameters are constrained by published experimental data. Model simulations are consistent with published experimental data, and the authors concluded that the mathematical modelling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signalling.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://ajpendo.physiology.org/cgi/content/abstract/283/5/E1084">A mathematical model of metabolic insulin signaling pathways</ulink>, Ahmad R. Sedaghat, Arthur Sherman, and Michael J. Quon, 2002, <ulink url="http://ajpendo.physiology.org/">
<emphasis>American Journal of Physiology</emphasis>
</ulink>, 283, E1084-E1101. (<ulink url="http://ajpendo.physiology.org/cgi/content/full/283/5/E1084">Full text</ulink> and <ulink url="http://ajpendo.physiology.org/cgi/reprint/283/5/E1084.pdf">PDF versions</ulink> of the article are available to subscribers on the American Journal of Physiology website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12376338&dopt=Abstract">PubMed ID: 12376338</ulink>
</para>
<para>
The raw CellML descriptions of the model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram</title>
</objectinfo>
<imagedata fileref="sedaghat_2002.png"/>
</imageobject>
</mediaobject>
<caption>Layout of the model elements.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!--
Below, we define some additional units for association with variables and
constants within the model. The identifiers are fairly self-explanatory.
-->
<units name="molar">
<unit units="litre" exponent="-1"/>
</units>
<units name="minute">
<unit units="second" multiplier="60.0"/>
</units>
<units name="flux">
<unit units="molar" exponent="1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="minute" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="molar" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<!--
The "environment" component is used to declare variables that are used by
all or most of the other components, in this case just "time".
-->
<component name="environment">
<variable units="minute" public_interface="out" name="time"/>
</component>
<!--
The following components describe all the reactants and products involved in the reactions.
-->
<component cmeta:id="insulin" name="insulin">
<variable units="molar" public_interface="out" name="insulin" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_insulin_rxn3"/>
<variable units="flux" public_interface="in" name="delta_insulin_rxn9"/>
<variable units="flux" public_interface="in" name="delta_insulin_rxn10"/>
<variable units="flux" public_interface="in" name="delta_insulin_rxn0"/>
<variable units="flux" public_interface="in" name="delta_insulin_rxn2"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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</bvar>
<ci>insulin</ci>
</apply>
<apply>
<plus/>
<ci>delta_insulin_rxn3</ci>
<ci>delta_insulin_rxn9</ci>
<ci>delta_insulin_rxn10</ci>
<ci>delta_insulin_rxn0</ci>
<ci>delta_insulin_rxn2</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="x2" name="x2">
<variable units="molar" public_interface="out" name="x2" initial_value="9.0E-13"/>
<variable units="flux" public_interface="in" name="delta_x2_rxn3"/>
<variable units="flux" public_interface="in" name="delta_x2_rxn0"/>
<variable units="flux" public_interface="in" name="delta_x2_rxn4"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>x2</ci>
</apply>
<apply>
<plus/>
<ci>delta_x2_rxn3</ci>
<ci>delta_x2_rxn0</ci>
<ci>delta_x2_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="x3" name="x3">
<variable units="molar" public_interface="out" name="x3" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x3_rxn0"/>
<variable units="flux" public_interface="in" name="delta_x3_rxn1"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<apply>
<diff/>
<bvar>
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</bvar>
<ci>x3</ci>
</apply>
<apply>
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<ci>delta_x3_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="x4" name="x4">
<variable units="molar" public_interface="out" name="x4" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x4_rxn2"/>
<variable units="flux" public_interface="in" name="delta_x4_rxn7"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>x4</ci>
</apply>
<apply>
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<ci>delta_x4_rxn7</ci>
</apply>
</apply>
</math>
</component>
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<variable units="molar" public_interface="out" name="x5" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x5_rxn1"/>
<variable units="flux" public_interface="in" name="delta_x5_rxn2"/>
<variable units="flux" public_interface="in" name="delta_x5_rxn3"/>
<variable units="flux" public_interface="in" name="delta_x5_rxn8"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>x5</ci>
</apply>
<apply>
<plus/>
<ci>delta_x5_rxn1</ci>
<ci>delta_x5_rxn2</ci>
<ci>delta_x5_rxn3</ci>
<ci>delta_x5_rxn8</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="x6" name="x6">
<variable units="molar" public_interface="out" name="x6" initial_value="1.0E-13"/>
<variable units="flux" public_interface="in" name="delta_x6_rxn4"/>
<variable units="flux" public_interface="in" name="delta_x6_rxn5"/>
<variable units="flux" public_interface="in" name="delta_x6_rxn9"/>
<variable units="flux" public_interface="in" name="delta_x6_rxn10"/>
<variable units="flux" public_interface="in" name="delta_x6_rxn6"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
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<ci>time</ci>
</bvar>
<ci>x6</ci>
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<apply>
<plus/>
<ci>delta_x6_rxn4</ci>
<ci>delta_x6_rxn5</ci>
<ci>delta_x6_rxn9</ci>
<ci>delta_x6_rxn10</ci>
<ci>delta_x6_rxn6</ci>
</apply>
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</math>
</component>
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<variable units="molar" public_interface="out" name="receptor_precursors" initial_value="1.0E-12"/>
<variable units="flux" public_interface="in" name="delta_receptor_precursors_rxn5"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
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<diff/>
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<ci>time</ci>
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<ci>receptor_precursors</ci>
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</apply>
</math>
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<component cmeta:id="degredation_products" name="degredation_products">
<variable units="molar" public_interface="out" name="degredation_products" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_degredation_products_rxn6"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
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<diff/>
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</bvar>
<ci>degredation_products</ci>
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<ci>delta_degredation_products_rxn6</ci>
</apply>
</math>
</component>
<component cmeta:id="x7" name="x7">
<variable units="molar" public_interface="out" name="x7" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x7_rxn7"/>
<variable units="flux" public_interface="in" name="delta_x7_rxn10"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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</bvar>
<ci>x7</ci>
</apply>
<apply>
<plus/>
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<ci>delta_x7_rxn10</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="x8" name="x8">
<variable units="molar" public_interface="out" name="x8" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x8_rxn8"/>
<variable units="flux" public_interface="in" name="delta_x8_rxn9"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>x8</ci>
</apply>
<apply>
<plus/>
<ci>delta_x8_rxn8</ci>
<ci>delta_x8_rxn9</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="IRS_1" name="IRS_1">
<variable units="molar" public_interface="out" name="IRS_1" initial_value="1.0E-12"/>
<variable units="flux" public_interface="in" name="delta_IRS_1_rxn11"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
</bvar>
<ci>IRS_1</ci>
</apply>
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</apply>
</math>
</component>
<component cmeta:id="IRS_1_P" name="IRS_1_P">
<variable units="molar" public_interface="out" name="IRS_1_P" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_IRS_1_P_rxn11"/>
<variable units="flux" public_interface="in" name="delta_IRS_1_P_rxn12"/>
<variable units="minute" public_interface="in" name="time"/>
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</apply>
</apply>
</math>
</component>
<component cmeta:id="PI3K" name="PI3K">
<variable units="molar" public_interface="out" name="PI3K" initial_value="1.0E-13"/>
<variable units="flux" public_interface="in" name="delta_PI3K_rxn12"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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</bvar>
<ci>PI3K</ci>
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</apply>
</math>
</component>
<component cmeta:id="IRS_1_P_PI3K" name="IRS_1_P_PI3K">
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<variable units="flux" public_interface="in" name="delta_IRS_1_P_PI3K_rxn12"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<ci>time</ci>
</bvar>
<ci>IRS_1_P_PI3K</ci>
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</apply>
</math>
</component>
<component cmeta:id="PI45P_2" name="PI45P_2">
<variable units="molar" public_interface="out" name="PI45P_2" initial_value="0.994E-12"/>
<variable units="flux" public_interface="in" name="delta_PI45P_2_rxn13"/>
<variable units="minute" public_interface="in" name="time"/>
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<ci>time</ci>
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<ci>PI45P_2</ci>
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</math>
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<component cmeta:id="PI345P_3" name="PI345P_3">
<variable units="molar" public_interface="out" name="PI345P_3" initial_value="0.31E-12"/>
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<variable units="flux" public_interface="in" name="delta_PI345P_3_rxn14"/>
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</component>
<component cmeta:id="x20_degredation_products" name="x20_degredation_products">
<variable units="molar" public_interface="out" name="x20_degredation_products" initial_value="0.0"/>
<variable units="flux" public_interface="in" name="delta_x20_degredation_products_rxn20"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>x20_degredation_products</ci>
</apply>
<ci>delta_x20_degredation_products_rxn20</ci>
</apply>
</math>
</component>
<component cmeta:id="PTP" name="PTP">
<variable units="molar" public_interface="out" name="PTP" initial_value="1.0"/>
</component>
<component cmeta:id="SHIP" name="SHIP">
<variable units="molar" public_interface="out" name="SHIP" initial_value="1.0"/>
</component>
<component cmeta:id="PTEN" name="PTEN">
<variable units="molar" public_interface="out" name="PTEN" initial_value="1.0"/>
</component>
<component cmeta:id="IRp" name="IRp">
<variable units="molar" public_interface="out" name="IRp" initial_value="8.97E-13"/>
</component>
<!--
The following components describe the reactions of the model.
-->
<component name="reaction0">
<variable units="molar" public_interface="in" name="x2"/>
<variable units="molar" public_interface="in" name="insulin"/>
<variable units="molar" public_interface="in" name="x3"/>
<variable units="flux" public_interface="out" name="delta_x2_rxn0"/>
<variable units="flux" public_interface="out" name="delta_insulin_rxn0"/>
<variable units="flux" public_interface="out" name="delta_x3_rxn0"/>
<variable units="second_order_rate_constant" name="k0" initial_value="6.0E7"/>
<variable units="first_order_rate_constant" name="k0_" initial_value="0.2"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x2">
<role stoichiometry="1" direction="forward" delta_variable="delta_x2_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="insulin">
<role stoichiometry="1" direction="forward" delta_variable="delta_insulin_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="x3">
<role stoichiometry="1" direction="forward" delta_variable="delta_x3_rxn0" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k0</ci>
<ci>x2</ci>
<ci>insulin</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k0_</ci>
<ci>x3</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction1">
<variable units="molar" public_interface="in" name="x3"/>
<variable units="molar" public_interface="in" name="x5"/>
<variable units="flux" public_interface="out" name="delta_x3_rxn1"/>
<variable units="flux" public_interface="out" name="delta_x5_rxn1"/>
<variable units="first_order_rate_constant" name="k1" initial_value="2500.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x3">
<role stoichiometry="1" delta_variable="delta_x3_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="x5">
<role stoichiometry="1" delta_variable="delta_x5_rxn1" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k1</ci>
<ci>x3</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction2">
<variable units="molar" public_interface="in" name="x5"/>
<variable units="molar" public_interface="in" name="insulin"/>
<variable units="molar" public_interface="in" name="x4"/>
<variable units="flux" public_interface="out" name="delta_x5_rxn2"/>
<variable units="flux" public_interface="out" name="delta_insulin_rxn2"/>
<variable units="flux" public_interface="out" name="delta_x4_rxn2"/>
<variable units="second_order_rate_constant" name="k2" initial_value="6.0E7"/>
<variable units="first_order_rate_constant" name="k2_" initial_value="20.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x5">
<role stoichiometry="1" direction="forward" delta_variable="delta_x5_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="insulin">
<role stoichiometry="1" direction="forward" delta_variable="delta_insulin_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="x4">
<role stoichiometry="1" direction="forward" delta_variable="delta_x4_rxn2" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>x5</ci>
<ci>insulin</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>x4</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="molar" public_interface="in" name="x5"/>
<variable units="molar" public_interface="in" name="insulin"/>
<variable units="molar" public_interface="in" name="x2"/>
<variable units="molar" public_interface="in" name="PTP"/>
<variable units="flux" public_interface="out" name="delta_x5_rxn3"/>
<variable units="flux" public_interface="out" name="delta_insulin_rxn3"/>
<variable units="flux" public_interface="out" name="delta_x2_rxn3"/>
<variable units="first_order_rate_constant" name="k3" initial_value="0.2"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x5">
<role stoichiometry="1" delta_variable="delta_x5_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="insulin">
<role stoichiometry="1" delta_variable="delta_insulin_rxn3" role="product"/>
</variable_ref>
<variable_ref variable="x2">
<role stoichiometry="1" delta_variable="delta_x2_rxn3" role="product"/>
</variable_ref>
<variable_ref variable="PTP">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k3</ci>
<ci>x5</ci>
<ci>PTP</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction4">
<variable units="molar" public_interface="in" name="x2"/>
<variable units="molar" public_interface="in" name="x6"/>
<variable units="flux" public_interface="out" name="delta_x2_rxn4"/>
<variable units="flux" public_interface="out" name="delta_x6_rxn4"/>
<variable units="first_order_rate_constant" name="k4" initial_value="3.3333E-4"/>
<variable units="first_order_rate_constant" name="k4_" initial_value="0.0030"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x2">
<role stoichiometry="1" direction="forward" delta_variable="delta_x2_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="x6">
<role stoichiometry="1" direction="forward" delta_variable="delta_x6_rxn4" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k4</ci>
<ci>x2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k4_</ci>
<ci>x6</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction5">
<variable units="molar" public_interface="in" name="receptor_precursors"/>
<variable units="molar" public_interface="in" name="x6"/>
<variable units="flux" public_interface="out" name="delta_receptor_precursors_rxn5"/>
<variable units="flux" public_interface="out" name="delta_x6_rxn5"/>
<variable units="first_order_rate_constant" name="k5" initial_value="1.67E-17"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="receptor_precursors">
<role stoichiometry="1" delta_variable="delta_receptor_precursors_rxn5" role="reactant"/>
</variable_ref>
<variable_ref variable="x6">
<role stoichiometry="1" delta_variable="delta_x6_rxn5" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k5</ci>
<ci>receptor_precursors</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction6">
<variable units="molar" public_interface="in" name="x6"/>
<variable units="molar" public_interface="in" name="degredation_products"/>
<variable units="flux" public_interface="out" name="delta_x6_rxn6"/>
<variable units="flux" public_interface="out" name="delta_degredation_products_rxn6"/>
<variable units="first_order_rate_constant" name="k6" initial_value="1.67E-18"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x6">
<role stoichiometry="1" delta_variable="delta_x6_rxn6" role="reactant"/>
</variable_ref>
<variable_ref variable="degredation_products">
<role stoichiometry="1" delta_variable="delta_degredation_products_rxn6" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k6</ci>
<ci>x6</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction7">
<variable units="molar" public_interface="in" name="x4"/>
<variable units="molar" public_interface="in" name="x7"/>
<variable units="flux" public_interface="out" name="delta_x4_rxn7"/>
<variable units="flux" public_interface="out" name="delta_x7_rxn7"/>
<variable units="first_order_rate_constant" name="k7" initial_value="0.0021"/>
<variable units="first_order_rate_constant" name="k7_" initial_value="2.1E-4"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x4">
<role stoichiometry="1" direction="forward" delta_variable="delta_x4_rxn7" role="reactant"/>
</variable_ref>
<variable_ref variable="x7">
<role stoichiometry="1" direction="forward" delta_variable="delta_x7_rxn7" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k7</ci>
<ci>x4</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k7_</ci>
<ci>x7</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction8">
<variable units="molar" public_interface="in" name="x5"/>
<variable units="molar" public_interface="in" name="x8"/>
<variable units="flux" public_interface="out" name="delta_x5_rxn8"/>
<variable units="flux" public_interface="out" name="delta_x8_rxn8"/>
<variable units="first_order_rate_constant" name="k8" initial_value="0.0021"/>
<variable units="first_order_rate_constant" name="k8_" initial_value="2.1E-4"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x5">
<role stoichiometry="1" direction="forward" delta_variable="delta_x5_rxn8" role="reactant"/>
</variable_ref>
<variable_ref variable="x8">
<role stoichiometry="1" direction="forward" delta_variable="delta_x8_rxn8" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k8</ci>
<ci>x5</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k8_</ci>
<ci>x8</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction9">
<variable units="molar" public_interface="in" name="x8"/>
<variable units="molar" public_interface="in" name="insulin"/>
<variable units="molar" public_interface="in" name="x6"/>
<variable units="molar" public_interface="in" name="PTP"/>
<variable units="flux" public_interface="out" name="delta_x8_rxn9"/>
<variable units="flux" public_interface="out" name="delta_insulin_rxn9"/>
<variable units="flux" public_interface="out" name="delta_x6_rxn9"/>
<variable units="first_order_rate_constant" name="k9" initial_value="0.461"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x8">
<role stoichiometry="1" delta_variable="delta_x8_rxn9" role="reactant"/>
</variable_ref>
<variable_ref variable="insulin">
<role stoichiometry="1" delta_variable="delta_insulin_rxn9" role="product"/>
</variable_ref>
<variable_ref variable="x6">
<role stoichiometry="1" delta_variable="delta_x6_rxn9" role="product"/>
</variable_ref>
<variable_ref variable="PTP">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k9</ci>
<ci>x8</ci>
<ci>PTP</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction10">
<variable units="molar" public_interface="in" name="x7"/>
<variable units="molar" public_interface="in" name="insulin"/>
<variable units="molar" public_interface="in" name="x6"/>
<variable units="molar" public_interface="in" name="PTP"/>
<variable units="flux" public_interface="out" name="delta_x7_rxn10"/>
<variable units="flux" public_interface="out" name="delta_insulin_rxn10"/>
<variable units="flux" public_interface="out" name="delta_x6_rxn10"/>
<variable units="first_order_rate_constant" name="k10" initial_value="0.461"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x7">
<role stoichiometry="1" delta_variable="delta_x7_rxn10" role="reactant"/>
</variable_ref>
<variable_ref variable="insulin">
<role stoichiometry="2" delta_variable="delta_insulin_rxn10" role="product"/>
</variable_ref>
<variable_ref variable="x6">
<role stoichiometry="1" delta_variable="delta_x6_rxn10" role="product"/>
</variable_ref>
<variable_ref variable="PTP">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k10</ci>
<ci>x7</ci>
<ci>PTP</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction11">
<variable units="molar" public_interface="in" name="IRS_1"/>
<variable units="molar" public_interface="in" name="IRS_1_P"/>
<variable units="molar" public_interface="in" name="PTP"/>
<variable units="molar" public_interface="in" name="x4"/>
<variable units="molar" public_interface="in" name="x5"/>
<variable units="molar" public_interface="in" name="IRp"/>
<variable units="flux" public_interface="out" name="delta_IRS_1_rxn11"/>
<variable units="flux" public_interface="out" name="delta_IRS_1_P_rxn11"/>
<variable units="first_order_rate_constant" name="k11" initial_value="4.16"/>
<variable units="first_order_rate_constant" name="k11_" initial_value="1.396"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="IRS_1">
<role stoichiometry="1" direction="forward" delta_variable="delta_IRS_1_rxn11" role="reactant"/>
</variable_ref>
<variable_ref variable="IRS_1_P">
<role stoichiometry="1" direction="forward" delta_variable="delta_IRS_1_P_rxn11" role="product"/>
</variable_ref>
<variable_ref variable="PTP">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="x4">
<role role="activator"/>
</variable_ref>
<variable_ref variable="x5">
<role role="activator"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>k11</ci>
<ci>IRS_1</ci>
<apply>
<plus/>
<ci>x4</ci>
<ci>x5</ci>
</apply>
</apply>
<ci>IRp</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k11_</ci>
<ci>IRS_1_P</ci>
<ci>PTP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction12">
<variable units="molar" public_interface="in" name="IRS_1_P"/>
<variable units="molar" public_interface="in" name="PI3K"/>
<variable units="molar" public_interface="in" name="IRS_1_P_PI3K"/>
<variable units="flux" public_interface="out" name="delta_IRS_1_P_rxn12"/>
<variable units="flux" public_interface="out" name="delta_PI3K_rxn12"/>
<variable units="flux" public_interface="out" name="delta_IRS_1_P_PI3K_rxn12"/>
<variable units="second_order_rate_constant" name="k12" initial_value="7.06E11"/>
<variable units="first_order_rate_constant" name="k12_" initial_value="10.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="IRS_1_P">
<role stoichiometry="1" direction="forward" delta_variable="delta_IRS_1_P_rxn12" role="reactant"/>
</variable_ref>
<variable_ref variable="PI3K">
<role stoichiometry="1" direction="forward" delta_variable="delta_PI3K_rxn12" role="reactant"/>
</variable_ref>
<variable_ref variable="IRS_1_P_PI3K">
<role stoichiometry="1" direction="forward" delta_variable="delta_IRS_1_P_PI3K_rxn12" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k12</ci>
<ci>IRS_1_P</ci>
<ci>PI3K</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k12_</ci>
<ci>IRS_1_P_PI3K</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction13">
<variable units="molar" public_interface="in" name="PI45P_2"/>
<variable units="molar" public_interface="in" name="PI345P_3"/>
<variable units="molar" public_interface="in" name="PI3K"/>
<variable units="molar" public_interface="in" name="PTEN"/>
<variable units="molar" public_interface="in" name="IRS_1_P_PI3K"/>
<variable units="flux" public_interface="out" name="delta_PI45P_2_rxn13"/>
<variable units="flux" public_interface="out" name="delta_PI345P_3_rxn13"/>
<variable units="first_order_rate_constant" name="k13"/>
<variable units="first_order_rate_constant" name="k13_" initial_value="42.148"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="PI45P_2">
<role stoichiometry="1" direction="forward" delta_variable="delta_PI45P_2_rxn13" role="reactant"/>
</variable_ref>
<variable_ref variable="PI345P_3">
<role stoichiometry="1" direction="forward" delta_variable="delta_PI345P_3_rxn13" role="product"/>
</variable_ref>
<variable_ref variable="PTEN">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k13</ci>
<ci>PI45P_2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k13_</ci>
<ci>PI345P_3</ci>
<ci>PTEN</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k13</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="first_order_rate_constant"> 1.39 </cn>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 0.31 </cn>
<cn cellml:units="dimensionless"> 99.4 </cn>
</apply>
<cn cellml:units="first_order_rate_constant"> 42.148 </cn>
</apply>
</apply>
<apply>
<divide/>
<ci> IRS_1_P_PI3K </ci>
<ci> PI3K </ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="first_order_rate_constant"> 1.39 </cn>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 0.31 </cn>
<cn cellml:units="dimensionless"> 99.4 </cn>
</apply>
<cn cellml:units="first_order_rate_constant"> 42.148 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reaction14">
<variable units="molar" public_interface="in" name="PI34P_2"/>
<variable units="molar" public_interface="in" name="PI345P_3"/>
<variable units="molar" public_interface="in" name="SHIP"/>
<variable units="flux" public_interface="out" name="delta_PI34P_2_rxn14"/>
<variable units="flux" public_interface="out" name="delta_PI345P_3_rxn14"/>
<variable units="first_order_rate_constant" name="k14" initial_value="2.961"/>
<variable units="first_order_rate_constant" name="k14_" initial_value="2.77"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="PI34P_2">
<role stoichiometry="1" direction="forward" delta_variable="delta_PI34P_2_rxn14" role="reactant"/>
</variable_ref>
<variable_ref variable="PI345P_3">
<role stoichiometry="1" direction="forward" delta_variable="delta_PI345P_3_rxn14" role="product"/>
</variable_ref>
<variable_ref variable="SHIP">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k14</ci>
<ci>PI34P_2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k14_</ci>
<ci>PI345P_3</ci>
<ci>SHIP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction15">
<variable units="molar" public_interface="in" name="Akt"/>
<variable units="molar" public_interface="in" name="Akt_P"/>
<variable units="molar" public_interface="in" name="PI345P_3"/>
<variable units="flux" public_interface="out" name="delta_Akt_rxn15"/>
<variable units="flux" public_interface="out" name="delta_Akt_P_rxn15"/>
<variable units="first_order_rate_constant" name="k15"/>
<variable units="first_order_rate_constant" name="k15_"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="Akt">
<role stoichiometry="1" direction="forward" delta_variable="delta_Akt_rxn15" role="reactant"/>
</variable_ref>
<variable_ref variable="Akt_P">
<role stoichiometry="1" direction="forward" delta_variable="delta_Akt_P_rxn15" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k15</ci>
<ci>Akt</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k15_</ci>
<ci>Akt_P</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k15</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1 </cn>
<ci> k15_ </ci>
</apply>
<apply>
<minus/>
<ci> PI345P_3 </ci>
<cn cellml:units="dimensionless"> 0.31 </cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 3.10 </cn>
<cn cellml:units="dimensionless"> 0.31 </cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>k15_</ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 10.0 </cn>
<apply>
<ln/>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reaction16">
<variable units="molar" public_interface="in" name="PKC"/>
<variable units="molar" public_interface="in" name="PKC_P"/>
<variable units="molar" public_interface="in" name="PI345P_3"/>
<variable units="flux" public_interface="out" name="delta_PKC_rxn16"/>
<variable units="flux" public_interface="out" name="delta_PKC_P_rxn16"/>
<variable units="first_order_rate_constant" name="k16" initial_value="1.0"/>
<variable units="first_order_rate_constant" name="k16_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="PKC">
<role stoichiometry="1" direction="forward" delta_variable="delta_PKC_rxn16" role="reactant"/>
</variable_ref>
<variable_ref variable="PKC_P">
<role stoichiometry="1" direction="forward" delta_variable="delta_PKC_P_rxn16" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k16</ci>
<ci>PKC</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k16_</ci>
<ci>PKC_P</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k16</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1 </cn>
<ci> k16_ </ci>
</apply>
<apply>
<minus/>
<ci> PI345P_3 </ci>
<cn cellml:units="dimensionless"> 0.31 </cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 3.10 </cn>
<cn cellml:units="dimensionless"> 0.31 </cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>k16_</ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 10.0 </cn>
<apply>
<ln/>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reaction17">
<variable units="molar" public_interface="in" name="x20"/>
<variable units="molar" public_interface="in" name="x21"/>
<variable units="flux" public_interface="out" name="delta_x20_rxn17"/>
<variable units="flux" public_interface="out" name="delta_x21_rxn17"/>
<variable units="first_order_rate_constant" name="k17"/>
<variable units="first_order_rate_constant" public_interface="out" name="k17_" initial_value="0.167"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="x20">
<role stoichiometry="1" direction="forward" delta_variable="delta_x20_rxn17" role="reactant"/>
</variable_ref>
<variable_ref variable="x21">
<role stoichiometry="1" direction="forward" delta_variable="delta_x21_rxn17" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k17</ci>
<ci>x20</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k17_</ci>
<ci>x21</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k17</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 4.0 </cn>
<cn cellml:units="dimensionless"> 96.0 </cn>
</apply>
<ci>k17_</ci>
</apply>
</apply>
</math>
</component>
<component name="reaction18">
<variable units="molar" public_interface="in" name="x20"/>
<variable units="molar" public_interface="in" name="x21"/>
<variable units="molar" public_interface="in" name="Akt_P"/>
<variable units="molar" public_interface="in" name="PKC_P"/>
<variable units="flux" public_interface="out" name="delta_x20_rxn18"/>
<variable units="flux" public_interface="out" name="delta_x21_rxn18"/>
<variable units="first_order_rate_constant" name="k18"/>
<variable units="dimensionless" name="effect"/>
<variable units="dimensionless" name="AP_equil"/>
<variable units="first_order_rate_constant" public_interface="in" name="k17_"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x20">
<role stoichiometry="1" delta_variable="delta_x20_rxn18" role="reactant"/>
</variable_ref>
<variable_ref variable="x21">
<role stoichiometry="1" delta_variable="delta_x21_rxn18" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k18</ci>
<ci>x20</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k18</ci>
<apply>
<times/>
<apply>
<minus/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 40.0 </cn>
<cn cellml:units="dimensionless"> 60.0 </cn>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 4.0 </cn>
<cn cellml:units="dimensionless"> 96.0 </cn>
</apply>
</apply>
<ci>k17_</ci>
<ci>effect</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>effect</ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.2 </cn>
<ci>Akt_P</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.8 </cn>
<ci>PKC_P</ci>
</apply>
</apply>
<ci>AP_equil</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>AP_equil</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 100.0 </cn>
<cn cellml:units="dimensionless"> 11.0 </cn>
</apply>
</apply>
</math>
</component>
<component name="reaction19">
<variable units="molar" public_interface="in" name="x20_precursors"/>
<variable units="molar" public_interface="in" name="x20"/>
<variable units="flux" public_interface="out" name="delta_x20_precursors_rxn19"/>
<variable units="flux" public_interface="out" name="delta_x20_rxn19"/>
<variable units="first_order_rate_constant" name="k19" initial_value="0.11088"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x20_precursors">
<role stoichiometry="1" delta_variable="delta_x20_precursors_rxn19" role="reactant"/>
</variable_ref>
<variable_ref variable="x20">
<role stoichiometry="1" delta_variable="delta_x20_rxn19" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k19</ci>
<ci>x20_precursors</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction20">
<variable units="molar" public_interface="in" name="x20"/>
<variable units="molar" public_interface="in" name="x20_degredation_products"/>
<variable units="flux" public_interface="out" name="delta_x20_rxn20"/>
<variable units="flux" public_interface="out" name="delta_x20_degredation_products_rxn20"/>
<variable units="first_order_rate_constant" name="k20" initial_value="0.001155"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="x20">
<role stoichiometry="1" delta_variable="delta_x20_rxn20" role="reactant"/>
</variable_ref>
<variable_ref variable="x20_degredation_products">
<role stoichiometry="1" delta_variable="delta_x20_degredation_products_rxn20" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k20</ci>
<ci>x20</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="reaction3" component_1="insulin"/>
<map_variables variable_2="insulin" variable_1="insulin"/>
<map_variables variable_2="delta_insulin_rxn3" variable_1="delta_insulin_rxn3"/>
</connection>
<connection>
<map_components component_2="reaction9" component_1="insulin"/>
<map_variables variable_2="insulin" variable_1="insulin"/>
<map_variables variable_2="delta_insulin_rxn9" variable_1="delta_insulin_rxn9"/>
</connection>
<connection>
<map_components component_2="reaction10" component_1="insulin"/>
<map_variables variable_2="insulin" variable_1="insulin"/>
<map_variables variable_2="delta_insulin_rxn10" variable_1="delta_insulin_rxn10"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="insulin"/>
<map_variables variable_2="insulin" variable_1="insulin"/>
<map_variables variable_2="delta_insulin_rxn0" variable_1="delta_insulin_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="insulin"/>
<map_variables variable_2="insulin" variable_1="insulin"/>
<map_variables variable_2="delta_insulin_rxn2" variable_1="delta_insulin_rxn2"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="x2"/>
<map_variables variable_2="x2" variable_1="x2"/>
<map_variables variable_2="delta_x2_rxn3" variable_1="delta_x2_rxn3"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="x2"/>
<map_variables variable_2="x2" variable_1="x2"/>
<map_variables variable_2="delta_x2_rxn0" variable_1="delta_x2_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="x2"/>
<map_variables variable_2="x2" variable_1="x2"/>
<map_variables variable_2="delta_x2_rxn4" variable_1="delta_x2_rxn4"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="x3"/>
<map_variables variable_2="x3" variable_1="x3"/>
<map_variables variable_2="delta_x3_rxn0" variable_1="delta_x3_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="x3"/>
<map_variables variable_2="x3" variable_1="x3"/>
<map_variables variable_2="delta_x3_rxn1" variable_1="delta_x3_rxn1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="x4"/>
<map_variables variable_2="x4" variable_1="x4"/>
<map_variables variable_2="delta_x4_rxn2" variable_1="delta_x4_rxn2"/>
</connection>
<connection>
<map_components component_2="reaction7" component_1="x4"/>
<map_variables variable_2="x4" variable_1="x4"/>
<map_variables variable_2="delta_x4_rxn7" variable_1="delta_x4_rxn7"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="x5"/>
<map_variables variable_2="x5" variable_1="x5"/>
<map_variables variable_2="delta_x5_rxn1" variable_1="delta_x5_rxn1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="x5"/>
<map_variables variable_2="x5" variable_1="x5"/>
<map_variables variable_2="delta_x5_rxn2" variable_1="delta_x5_rxn2"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="x5"/>
<map_variables variable_2="x5" variable_1="x5"/>
<map_variables variable_2="delta_x5_rxn3" variable_1="delta_x5_rxn3"/>
</connection>
<connection>
<map_components component_2="reaction8" component_1="x5"/>
<map_variables variable_2="x5" variable_1="x5"/>
<map_variables variable_2="delta_x5_rxn8" variable_1="delta_x5_rxn8"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="x6"/>
<map_variables variable_2="x6" variable_1="x6"/>
<map_variables variable_2="delta_x6_rxn4" variable_1="delta_x6_rxn4"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="x6"/>
<map_variables variable_2="x6" variable_1="x6"/>
<map_variables variable_2="delta_x6_rxn5" variable_1="delta_x6_rxn5"/>
</connection>
<connection>
<map_components component_2="reaction9" component_1="x6"/>
<map_variables variable_2="x6" variable_1="x6"/>
<map_variables variable_2="delta_x6_rxn9" variable_1="delta_x6_rxn9"/>
</connection>
<connection>
<map_components component_2="reaction10" component_1="x6"/>
<map_variables variable_2="x6" variable_1="x6"/>
<map_variables variable_2="delta_x6_rxn10" variable_1="delta_x6_rxn10"/>
</connection>
<connection>
<map_components component_2="reaction6" component_1="x6"/>
<map_variables variable_2="x6" variable_1="x6"/>
<map_variables variable_2="delta_x6_rxn6" variable_1="delta_x6_rxn6"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="receptor_precursors"/>
<map_variables variable_2="receptor_precursors" variable_1="receptor_precursors"/>
<map_variables variable_2="delta_receptor_precursors_rxn5" variable_1="delta_receptor_precursors_rxn5"/>
</connection>
<connection>
<map_components component_2="reaction6" component_1="degredation_products"/>
<map_variables variable_2="degredation_products" variable_1="degredation_products"/>
<map_variables variable_2="delta_degredation_products_rxn6" variable_1="delta_degredation_products_rxn6"/>
</connection>
<connection>
<map_components component_2="reaction7" component_1="x7"/>
<map_variables variable_2="x7" variable_1="x7"/>
<map_variables variable_2="delta_x7_rxn7" variable_1="delta_x7_rxn7"/>
</connection>
<connection>
<map_components component_2="reaction10" component_1="x7"/>
<map_variables variable_2="x7" variable_1="x7"/>
<map_variables variable_2="delta_x7_rxn10" variable_1="delta_x7_rxn10"/>
</connection>
<connection>
<map_components component_2="reaction8" component_1="x8"/>
<map_variables variable_2="x8" variable_1="x8"/>
<map_variables variable_2="delta_x8_rxn8" variable_1="delta_x8_rxn8"/>
</connection>
<connection>
<map_components component_2="reaction9" component_1="x8"/>
<map_variables variable_2="x8" variable_1="x8"/>
<map_variables variable_2="delta_x8_rxn9" variable_1="delta_x8_rxn9"/>
</connection>
<connection>
<map_components component_2="reaction11" component_1="IRS_1"/>
<map_variables variable_2="IRS_1" variable_1="IRS_1"/>
<map_variables variable_2="delta_IRS_1_rxn11" variable_1="delta_IRS_1_rxn11"/>
</connection>
<connection>
<map_components component_2="reaction11" component_1="IRS_1_P"/>
<map_variables variable_2="IRS_1_P" variable_1="IRS_1_P"/>
<map_variables variable_2="delta_IRS_1_P_rxn11" variable_1="delta_IRS_1_P_rxn11"/>
</connection>
<connection>
<map_components component_2="reaction12" component_1="IRS_1_P"/>
<map_variables variable_2="IRS_1_P" variable_1="IRS_1_P"/>
<map_variables variable_2="delta_IRS_1_P_rxn12" variable_1="delta_IRS_1_P_rxn12"/>
</connection>
<connection>
<map_components component_2="reaction12" component_1="PI3K"/>
<map_variables variable_2="PI3K" variable_1="PI3K"/>
<map_variables variable_2="delta_PI3K_rxn12" variable_1="delta_PI3K_rxn12"/>
</connection>
<connection>
<map_components component_2="reaction13" component_1="PI3K"/>
<map_variables variable_2="PI3K" variable_1="PI3K"/>
</connection>
<connection>
<map_components component_2="reaction13" component_1="IRS_1_P_PI3K"/>
<map_variables variable_2="IRS_1_P_PI3K" variable_1="IRS_1_P_PI3K"/>
</connection>
<connection>
<map_components component_2="reaction12" component_1="IRS_1_P_PI3K"/>
<map_variables variable_2="IRS_1_P_PI3K" variable_1="IRS_1_P_PI3K"/>
<map_variables variable_2="delta_IRS_1_P_PI3K_rxn12" variable_1="delta_IRS_1_P_PI3K_rxn12"/>
</connection>
<connection>
<map_components component_2="reaction13" component_1="PI45P_2"/>
<map_variables variable_2="PI45P_2" variable_1="PI45P_2"/>
<map_variables variable_2="delta_PI45P_2_rxn13" variable_1="delta_PI45P_2_rxn13"/>
</connection>
<connection>
<map_components component_2="reaction15" component_1="PI345P_3"/>
<map_variables variable_2="PI345P_3" variable_1="PI345P_3"/>
</connection>
<connection>
<map_components component_2="reaction16" component_1="PI345P_3"/>
<map_variables variable_2="PI345P_3" variable_1="PI345P_3"/>
</connection>
<connection>
<map_components component_2="reaction13" component_1="PI345P_3"/>
<map_variables variable_2="PI345P_3" variable_1="PI345P_3"/>
<map_variables variable_2="delta_PI345P_3_rxn13" variable_1="delta_PI345P_3_rxn13"/>
</connection>
<connection>
<map_components component_2="reaction14" component_1="PI345P_3"/>
<map_variables variable_2="PI345P_3" variable_1="PI345P_3"/>
<map_variables variable_2="delta_PI345P_3_rxn14" variable_1="delta_PI345P_3_rxn14"/>
</connection>
<connection>
<map_components component_2="reaction14" component_1="PI34P_2"/>
<map_variables variable_2="PI34P_2" variable_1="PI34P_2"/>
<map_variables variable_2="delta_PI34P_2_rxn14" variable_1="delta_PI34P_2_rxn14"/>
</connection>
<connection>
<map_components component_2="reaction15" component_1="Akt"/>
<map_variables variable_2="Akt" variable_1="Akt"/>
<map_variables variable_2="delta_Akt_rxn15" variable_1="delta_Akt_rxn15"/>
</connection>
<connection>
<map_components component_2="reaction15" component_1="Akt_P"/>
<map_variables variable_2="Akt_P" variable_1="Akt_P"/>
<map_variables variable_2="delta_Akt_P_rxn15" variable_1="delta_Akt_P_rxn15"/>
</connection>
<connection>
<map_components component_2="reaction18" component_1="Akt_P"/>
<map_variables variable_2="Akt_P" variable_1="Akt_P"/>
</connection>
<connection>
<map_components component_2="reaction16" component_1="PKC"/>
<map_variables variable_2="PKC" variable_1="PKC"/>
<map_variables variable_2="delta_PKC_rxn16" variable_1="delta_PKC_rxn16"/>
</connection>
<connection>
<map_components component_2="reaction16" component_1="PKC_P"/>
<map_variables variable_2="PKC_P" variable_1="PKC_P"/>
<map_variables variable_2="delta_PKC_P_rxn16" variable_1="delta_PKC_P_rxn16"/>
</connection>
<connection>
<map_components component_2="reaction18" component_1="PKC_P"/>
<map_variables variable_2="PKC_P" variable_1="PKC_P"/>
</connection>
<connection>
<map_components component_2="reaction19" component_1="x20"/>
<map_variables variable_2="x20" variable_1="x20"/>
<map_variables variable_2="delta_x20_rxn19" variable_1="delta_x20_rxn19"/>
</connection>
<connection>
<map_components component_2="reaction17" component_1="x20"/>
<map_variables variable_2="x20" variable_1="x20"/>
<map_variables variable_2="delta_x20_rxn17" variable_1="delta_x20_rxn17"/>
</connection>
<connection>
<map_components component_2="reaction18" component_1="x20"/>
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This is the CellML descripition of Sedaghat, Sherman and Quon's 2002
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Added publication date information.
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The University of Auckland, Bioengineering Institute
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A mathematical model of metabolic insulin signaling pathways
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Sedaghat, Sherman and Quon's 2002 mathematical model of metabolic
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