- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-04-28 13:02:00+12:00
- Desc:
- Minor changes to RDF and documentation.
- Permanent Source URI:
- https://models.cellml.org/workspace/sedaghat_sherman_quon_2002/rawfile/df674a837879e0cf341dffc36e830e5baea13114/sedaghat_sherman_quon_2002_feedback.cellml
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<!--
This CellML file was generated on 20/04/2010 at 9:27:31 at a.m. using:
COR (0.9.31.1371)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
-->
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<title>A Mathematical Model of Metabolic Insulin Signalling Pathways</title>
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<firstname>Catherine</firstname>
<surname>Lloyd</surname>
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<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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<section id="sec_status">
<title>Model Status</title>
<para>
This model runs in PCEnv, OpenCell and COR and the units are consistent throughout. It describes the complete model with feedback, and it is a close match to figures 8 and 9. However, a time delay was ignored in the eqaution for PKC, which prevents the model from completely matching the paper.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: We develop a mathematical model that explicitly represents many of the known signaling components mediating translocation of the insulin-responsive glucose transporter GLUT4 to gain insight into the complexities of metabolic insulin signaling pathways. A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate-1, activation of phosphatidylinositol 3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C-zeta is coupled with previously validated subsystem models of insulin receptor binding, receptor recycling, and GLUT4 translocation. A system of differential equations is defined by the structure of the model. Rate constants and model parameters are constrained by published experimental data. Model simulations of insulin dose-response experiments agree with published experimental data and also generate expected qualitative behaviors such as sequential signal amplification and increased sensitivity of downstream components. We examined the consequences of incorporating feedback pathways as well as representing pathological conditions, such as increased levels of protein tyrosine phosphatases, to illustrate the utility of our model for exploring molecular mechanisms. We conclude that mathematical modeling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signaling.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
A mathematical model of metabolic insulin signaling pathways, Ahmad R. Sedaghat, Arthur Sherman, and Michael J. Quon, 2002,<emphasis>American Journal of Physiology</emphasis>, 283, E1084-E1101. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12376338&dopt=Abstract">PubMed ID: 12376338</ulink>
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Sedaghat, Sherman and Quon's 2002 mathematical model of metabolic insulin signaling pathways.
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<map_variables variable_1="k6" variable_2="k6"/>
<map_variables variable_1="PTP" variable_2="PTP"/>
<map_variables variable_1="x7" variable_2="x7"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x8" component_2="reaction_constants"/>
<map_variables variable_1="k4b" variable_2="k4b"/>
<map_variables variable_1="k_minus4b" variable_2="k_minus4b"/>
<map_variables variable_1="k6" variable_2="k6"/>
<map_variables variable_1="PTP" variable_2="PTP"/>
<map_variables variable_1="x8" variable_2="x8"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x9" component_2="reaction_constants"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k_minus7" variable_2="k_minus7"/>
<map_variables variable_1="k7b" variable_2="k7b"/>
<map_variables variable_1="k_minus7b" variable_2="k_minus7b"/>
<map_variables variable_1="IRp" variable_2="IRp"/>
<map_variables variable_1="PTP" variable_2="PTP"/>
<map_variables variable_1="PKC" variable_2="PKC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x10" component_2="reaction_constants"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k_minus7" variable_2="k_minus7"/>
<map_variables variable_1="k8" variable_2="k8"/>
<map_variables variable_1="k_minus8" variable_2="k_minus8"/>
<map_variables variable_1="IRp" variable_2="IRp"/>
<map_variables variable_1="PTP" variable_2="PTP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x10a" component_2="reaction_constants"/>
<map_variables variable_1="k7b" variable_2="k7b"/>
<map_variables variable_1="k_minus7b" variable_2="k_minus7b"/>
<map_variables variable_1="PKC" variable_2="PKC"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x11" component_2="reaction_constants"/>
<map_variables variable_1="k8" variable_2="k8"/>
<map_variables variable_1="k_minus8" variable_2="k_minus8"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x12" component_2="reaction_constants"/>
<map_variables variable_1="k8" variable_2="k8"/>
<map_variables variable_1="k_minus8" variable_2="k_minus8"/>
<map_variables variable_1="x12" variable_2="x12"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x13" component_2="reaction_constants"/>
<map_variables variable_1="k9" variable_2="k9"/>
<map_variables variable_1="k_minus9" variable_2="k_minus9"/>
<map_variables variable_1="k10" variable_2="k10"/>
<map_variables variable_1="k_minus10" variable_2="k_minus10"/>
<map_variables variable_1="PTEN" variable_2="PTEN"/>
<map_variables variable_1="SHIP" variable_2="SHIP"/>
<map_variables variable_1="x13" variable_2="x13"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x14" component_2="reaction_constants"/>
<map_variables variable_1="k9" variable_2="k9"/>
<map_variables variable_1="k_minus9" variable_2="k_minus9"/>
<map_variables variable_1="PTEN" variable_2="PTEN"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x15" component_2="reaction_constants"/>
<map_variables variable_1="k10" variable_2="k10"/>
<map_variables variable_1="k_minus10" variable_2="k_minus10"/>
<map_variables variable_1="SHIP" variable_2="SHIP"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x16" component_2="reaction_constants"/>
<map_variables variable_1="k11" variable_2="k11"/>
<map_variables variable_1="k_minus11" variable_2="k_minus11"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x17" component_2="reaction_constants"/>
<map_variables variable_1="k11" variable_2="k11"/>
<map_variables variable_1="k_minus11" variable_2="k_minus11"/>
<map_variables variable_1="x17" variable_2="x17"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x18" component_2="reaction_constants"/>
<map_variables variable_1="k12" variable_2="k12"/>
<map_variables variable_1="k_minus12" variable_2="k_minus12"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x19" component_2="reaction_constants"/>
<map_variables variable_1="k12" variable_2="k12"/>
<map_variables variable_1="k_minus12" variable_2="k_minus12"/>
<map_variables variable_1="x19" variable_2="x19"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x20" component_2="reaction_constants"/>
<map_variables variable_1="k13" variable_2="k13"/>
<map_variables variable_1="k_minus13" variable_2="k_minus13"/>
<map_variables variable_1="k13b" variable_2="k13b"/>
<map_variables variable_1="k14" variable_2="k14"/>
<map_variables variable_1="k_minus14" variable_2="k_minus14"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="x21" component_2="reaction_constants"/>
<map_variables variable_1="k13" variable_2="k13"/>
<map_variables variable_1="k_minus13" variable_2="k_minus13"/>
<map_variables variable_1="k13b" variable_2="k13b"/>
</connection>
</model>
