- Author:
- AnandR <a.rampadarath@auckland.ac.nz>
- Date:
- 2019-09-11 12:10:19+12:00
- Desc:
- added .omex files
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/598/rawfile/2f750bf5ebed3a930bd535e0fb2ac4c3214b42d1/model/MacKenzie_1996.cellml
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<article>
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<title>Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2</title>
<author>
<firstname>Jonna</firstname>
<surname>Terkildsen</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
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<title>Model Status</title>
<para>This CellML model has been curated, the units are consistent and the model runs in COR and PCEnv. This model recreates the published results.</para>
</sect1>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>Abstract: The Na-dependent, low affinity glucose transporter SGLT2 cloned from pig kidney is 76% identical (at the amino acid level) to its high affinity homologue SGLT1. Using two-microelectrode voltage clamp, we have characterized the presteady-state and steady-state kinetics of SGLT2 expressed in Xenopus oocytes. The kinetic properties of the steady-state sugar-evoked currents as a function of external Na and a-methyl-D-glucopyranoside (aMG) concentrations were consistent with an ordered, simultaneous transport model in which Na binds first. Na binding was voltage-dependent and saturated with hyperpolarizing voltages. Phlorizin was a potent inhibitor of the sugar-evoked currents (Ki ~10 mM) and blocked an inward Na current in the absence of sugar. SGLT2 exhibited Na-dependent presteadystate currents with time constants 3-7 ms. Charge movements were described by Boltzmann relations with apparent valence ~1 and maximal charge transfer ~11 nC, and were reduced by the addition of sugar or phlorizin. The differences between SGLT1 and SGLT2 were that (i) the apparent affinity constant (K0.5) for aMG (~3 mM) was an order of magnitude higher for SGLT2; (ii) SGLT2 excluded galactose, suggesting discrete sugar binding; (iii) K0.5 for Na was lower in SGLT2; and (iv) the Hill coefficient for Na was 1 for SGLT2 but 2 for SGLT1. Simulations of the six-state kinetic model previously proposed for SGLT1 indicated that many of the kinetic properties observed in SGLT2 are expected by simply reducing the Na/glucose coupling from 2 to 1.</para>
<para>The original paper reference is cited below:</para>
<para>
Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2, M. Mackenzie, D.D.F. Loo, M. Panayotova-Heiermann, and E. M. Wright, 1996,
<emphasis>Journal of Biological Chemistry</emphasis>
, 271, 32678-32683.
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8955098&query_hl=1&itool=pubmed_docsum">PubMed ID: 8955098</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<title>model diagram</title>
</objectinfo>
<imagedata fileref="mackenzie_1996.png" />
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</mediaobject>
<caption>Schematic diagram of the Mackenzie et al 1996 SGLT2 model. C' represents the external-facing carrier. C'' represents the internal-facing carrier.</caption>
</informalfigure>
</sect1>
</article>
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<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>C5_sum</ci>
<apply>
<plus />
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_61</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>C6_sum</ci>
<apply>
<plus />
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>C_sum</ci>
<apply>
<plus />
<ci>C1_sum</ci>
<ci>C2_sum</ci>
<ci>C3_sum</ci>
<ci>C4_sum</ci>
<ci>C5_sum</ci>
<ci>C6_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C1</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C1_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C2</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C2_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C3</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C3_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C4</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C4_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C5</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C5_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
<apply>
<eq />
<ci>C6</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>C6_sum</ci>
</apply>
<ci>C_sum</ci>
</apply>
</apply>
</math>
</component>
<component name="NBC_current">
<variable cmeta:id="NBC_current.C_3" name="C_3" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C_4" name="C_4" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C_1" name="C_1" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C_2" name="C_2" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C_5" name="C_5" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.k_61" name="k_61" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.C_6" name="C_6" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.k_21" name="k_21" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.k_43" name="k_43" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.k_65" name="k_65" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.I_NaGl_SS" name="I_NaGl_SS" public_interface="out" units="uA" />
<variable cmeta:id="NBC_current.delta" name="delta" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.k_25" name="k_25" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.alpha_p" name="alpha_p" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.C6" name="C6" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C5" name="C5" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C4" name="C4" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C3" name="C3" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C2" name="C2" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.C1" name="C1" public_interface="in" units="umol" />
<variable cmeta:id="NBC_current.alpha_pp" name="alpha_pp" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.k_52" name="k_52" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.z_Na" name="z_Na" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.k_12" name="k_12" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.k_34" name="k_34" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.k_56" name="k_56" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.z_c" name="z_c" public_interface="in" units="dimensionless" />
<variable cmeta:id="NBC_current.k_16" name="k_16" public_interface="in" units="per_second" />
<variable cmeta:id="NBC_current.J_Na" name="J_Na" public_interface="out" units="umol_per_second" />
<variable cmeta:id="NBC_current.F" name="F" public_interface="in" units="C_per_mol" />
<variable cmeta:id="NBC_current.I_NaGl_pSS" name="I_NaGl_pSS" public_interface="out" units="uA" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>I_NaGl_pSS</ci>
<apply>
<times />
<apply>
<minus />
<ci>F</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>n</ci>
<ci>z_Na</ci>
<ci>alpha_p</ci>
<apply>
<minus />
<apply>
<times />
<ci>k_12</ci>
<ci>C_1</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>C_2</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<ci>z_c</ci>
<ci>delta</ci>
<apply>
<minus />
<apply>
<times />
<ci>k_16</ci>
<ci>C_1</ci>
</apply>
<apply>
<times />
<ci>k_61</ci>
<ci>C_6</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<ci>n</ci>
<ci>z_Na</ci>
<ci>alpha_pp</ci>
<apply>
<minus />
<apply>
<times />
<ci>k_56</ci>
<ci>C_5</ci>
</apply>
<apply>
<times />
<ci>k_65</ci>
<ci>C_6</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>I_NaGl_SS</ci>
<apply>
<times />
<apply>
<minus />
<ci>F</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>z_c</ci>
<apply>
<minus />
<apply>
<times />
<ci>k_16</ci>
<ci>C1</ci>
</apply>
<apply>
<times />
<ci>k_61</ci>
<ci>C6</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>z_c</ci>
<apply>
<times />
<ci>z_Na</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>k_25</ci>
<ci>C2</ci>
</apply>
<apply>
<times />
<ci>k_52</ci>
<ci>C5</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>z_c</ci>
<apply>
<times />
<ci>z_Na</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>k_34</ci>
<ci>C3</ci>
</apply>
<apply>
<times />
<ci>k_43</ci>
<ci>C4</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>J_Na</ci>
<apply>
<plus />
<apply>
<minus />
<apply>
<times />
<ci>k_25</ci>
<ci>C2</ci>
</apply>
<apply>
<times />
<ci>k_52</ci>
<ci>C5</ci>
</apply>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>k_34</ci>
<ci>C3</ci>
</apply>
<apply>
<times />
<ci>k_43</ci>
<ci>C4</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rate_constants">
<variable cmeta:id="rate_constants.k0_32" name="k0_32" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k0_54" name="k0_54" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="rate_constants.ks_12" name="ks_12" public_interface="out" units="per_M_per_second" />
<variable cmeta:id="rate_constants.alpha_pp" name="alpha_pp" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.k0_52" name="k0_52" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.glucose_o" name="glucose_o" public_interface="in" units="M" />
<variable cmeta:id="rate_constants.k0_12" name="k0_12" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="rate_constants.k0_34" name="k0_34" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k0_56" name="k0_56" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.z_c" name="z_c" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.k_32" name="k_32" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_54" name="k_54" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.z_Na" name="z_Na" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.delta" name="delta" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.k_12" name="k_12" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_34" name="k_34" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_56" name="k_56" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_16" name="k_16" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.Na_i" name="Na_i" public_interface="in" units="M" />
<variable cmeta:id="rate_constants.k_52" name="k_52" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_52_temp" name="k_52_temp" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k0_54_temp" name="k0_54_temp" public_interface="out" units="per_M_per_second" />
<variable cmeta:id="rate_constants.k0_21" name="k0_21" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k0_43" name="k0_43" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k0_65" name="k0_65" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="rate_constants.k0_25" name="k0_25" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k0_23" name="k0_23" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="rate_constants.k0_45" name="k0_45" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k_21" name="k_21" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_43" name="k_43" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_65" name="k_65" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.Na_o" name="Na_o" public_interface="in" units="M" />
<variable cmeta:id="rate_constants.k_23" name="k_23" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k_45" name="k_45" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k0_61" name="k0_61" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.k_25" name="k_25" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.mu" name="mu" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.alpha_p" name="alpha_p" public_interface="in" units="dimensionless" />
<variable cmeta:id="rate_constants.k_61" name="k_61" public_interface="out" units="per_second" />
<variable cmeta:id="rate_constants.k0_16" name="k0_16" public_interface="in" units="per_second" />
<variable cmeta:id="rate_constants.C_T" name="C_T" public_interface="in" units="umol" />
<variable cmeta:id="rate_constants.glucose_i" name="glucose_i" public_interface="in" units="M" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>ks_12</ci>
<apply>
<times />
<ci>k0_12</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<minus />
<ci>n</ci>
</apply>
<ci>alpha_p</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_12</ci>
<apply>
<times />
<ci>ks_12</ci>
<apply>
<power />
<ci>Na_o</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_21</ci>
<apply>
<times />
<ci>k0_21</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<ci>n</ci>
<ci>z_Na</ci>
<ci>alpha_p</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_23</ci>
<apply>
<times />
<ci>k0_23</ci>
<ci>glucose_o</ci>
</apply>
</apply>
<apply>
<eq />
<ci>k_32</ci>
<ci>k0_32</ci>
</apply>
<apply>
<eq />
<ci>k_34</ci>
<apply>
<times />
<ci>k0_34</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<minus />
<apply>
<plus />
<ci>z_c</ci>
<ci>n</ci>
</apply>
</apply>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_43</ci>
<apply>
<times />
<ci>k0_43</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<plus />
<ci>z_c</ci>
<ci>n</ci>
</apply>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_45</ci>
<ci>k0_45</ci>
</apply>
<apply>
<eq />
<ci>k_54</ci>
<apply>
<times />
<ci>k0_54_temp</ci>
<ci>glucose_i</ci>
</apply>
</apply>
<apply>
<eq />
<ci>k_25</ci>
<apply>
<times />
<ci>k0_25</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<minus />
<apply>
<plus />
<ci>z_c</ci>
<ci>n</ci>
</apply>
</apply>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_52_temp</ci>
<apply>
<times />
<ci>k0_52</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<plus />
<ci>z_c</ci>
<ci>n</ci>
</apply>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_56</ci>
<apply>
<times />
<ci>k0_56</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<minus />
<ci>n</ci>
</apply>
<ci>z_Na</ci>
<ci>alpha_pp</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_65</ci>
<apply>
<times />
<ci>k0_65</ci>
<apply>
<power />
<ci>Na_i</ci>
<ci>n</ci>
</apply>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<ci>n</ci>
<ci>z_Na</ci>
<ci>alpha_pp</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_61</ci>
<apply>
<times />
<ci>k0_61</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<ci>z_c</ci>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_16</ci>
<apply>
<times />
<ci>k0_16</ci>
<apply>
<exp />
<apply>
<divide />
<apply>
<times />
<apply>
<minus />
<ci>z_c</ci>
</apply>
<ci>delta</ci>
<ci>mu</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k_52</ci>
<apply>
<divide />
<apply>
<times />
<ci>k0_12</ci>
<ci>k_25</ci>
<ci>k0_56</ci>
<ci>k0_61</ci>
</apply>
<apply>
<times />
<ci>k0_21</ci>
<ci>k0_16</ci>
<ci>k0_65</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>k0_54_temp</ci>
<apply>
<divide />
<apply>
<times />
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
</apply>
<apply>
<times />
<ci>k_43</ci>
<ci>k_32</ci>
<ci>k_25</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="phenomonological_constants">
<variable cmeta:id="phenomonological_constants.Khalf_Na" name="Khalf_Na" public_interface="out" units="M" />
<variable cmeta:id="phenomonological_constants.alpha" name="alpha" public_interface="out" units="M2" />
<variable cmeta:id="phenomonological_constants.F" name="F" public_interface="in" units="C_per_mol" />
<variable cmeta:id="phenomonological_constants.Imax_Na" name="Imax_Na" public_interface="out" units="uA" />
<variable cmeta:id="phenomonological_constants.gamma" name="gamma" public_interface="out" units="M2_per_second" />
<variable cmeta:id="phenomonological_constants.beta" name="beta" public_interface="out" units="M" />
<variable cmeta:id="phenomonological_constants.k_12" name="k_12" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_34" name="k_34" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_56" name="k_56" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.lambda" name="lambda" public_interface="out" units="per_M2_per_second5" />
<variable cmeta:id="phenomonological_constants.glucose_o" name="glucose_o" public_interface="in" units="M" />
<variable cmeta:id="phenomonological_constants.k_32" name="k_32" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_54" name="k_54" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.Na_o" name="Na_o" public_interface="in" units="M" />
<variable cmeta:id="phenomonological_constants.phi" name="phi" public_interface="out" units="M_per_second" />
<variable cmeta:id="phenomonological_constants.k_16" name="k_16" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k0_23" name="k0_23" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="phenomonological_constants.k_52" name="k_52" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.Khalf_gluc" name="Khalf_gluc" public_interface="out" units="M" />
<variable cmeta:id="phenomonological_constants.chi" name="chi" public_interface="out" units="M" />
<variable cmeta:id="phenomonological_constants.Imax_gluc" name="Imax_gluc" public_interface="out" units="uA" />
<variable cmeta:id="phenomonological_constants.C_T" name="C_T" public_interface="in" units="umol" />
<variable cmeta:id="phenomonological_constants.k_23" name="k_23" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_45" name="k_45" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_21" name="k_21" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_43" name="k_43" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_65" name="k_65" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.k_25" name="k_25" public_interface="in" units="per_second" />
<variable cmeta:id="phenomonological_constants.epsilon" name="epsilon" public_interface="out" units="per_second" />
<variable cmeta:id="phenomonological_constants.ks_12" name="ks_12" public_interface="in" units="per_M_per_second" />
<variable cmeta:id="phenomonological_constants.k_61" name="k_61" public_interface="in" units="per_second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>lambda</ci>
<apply>
<plus />
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_43</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>chi</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>beta</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_34</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k0_23</ci>
<ci>k_16</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>alpha</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>gamma</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_54</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
<apply>
<times />
<ci>k_16</ci>
<ci>k_21</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_52</ci>
<ci>k_65</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>phi</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<minus />
<apply>
<minus />
<apply>
<times />
<apply>
<minus />
<ci>ks_12</ci>
</apply>
<ci>k_25</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
</apply>
<apply>
<times />
<ci>ks_12</ci>
<ci>k_25</ci>
<ci>k_32</ci>
<ci>k_43</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>epsilon</ci>
<apply>
<times />
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>lambda</ci>
</apply>
<apply>
<minus />
<ci>ks_12</ci>
</apply>
<ci>k0_23</ci>
<ci>k_34</ci>
<ci>k_45</ci>
<ci>k_56</ci>
<ci>k_61</ci>
</apply>
</apply>
<apply>
<eq />
<ci>Imax_gluc</ci>
<apply>
<divide />
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F</ci>
<ci>C_T</ci>
<ci>epsilon</ci>
<ci>Na_o</ci>
</apply>
<apply>
<plus />
<ci>beta</ci>
<ci>Na_o</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>Imax_Na</ci>
<apply>
<divide />
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F</ci>
<ci>C_T</ci>
<apply>
<plus />
<ci>phi</ci>
<apply>
<times />
<ci>epsilon</ci>
<ci>glucose_o</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<ci>chi</ci>
<ci>glucose_o</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>Khalf_gluc</ci>
<apply>
<divide />
<apply>
<plus />
<ci>alpha</ci>
<apply>
<times />
<ci>chi</ci>
<ci>Na_o</ci>
</apply>
</apply>
<apply>
<plus />
<ci>beta</ci>
<ci>Na_o</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>Khalf_Na</ci>
<apply>
<divide />
<apply>
<plus />
<ci>alpha</ci>
<apply>
<times />
<ci>beta</ci>
<ci>glucose_o</ci>
</apply>
</apply>
<apply>
<plus />
<ci>chi</ci>
<ci>glucose_o</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="kinetic_equations">
<variable cmeta:id="kinetic_equations.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="kinetic_equations.C_6_temp" name="C_6_temp" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.k_52" name="k_52" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_61" name="k_61" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_16" name="k_16" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_25" name="k_25" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_12" name="k_12" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_23" name="k_23" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_34" name="k_34" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_45" name="k_45" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_56" name="k_56" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_21" name="k_21" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_32" name="k_32" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_43" name="k_43" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_54" name="k_54" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.k_65" name="k_65" public_interface="in" units="per_second" />
<variable cmeta:id="kinetic_equations.C_6" name="C_6" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.C_5" name="C_5" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.C_4" name="C_4" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.C_T" name="C_T" public_interface="in" units="umol" />
<variable cmeta:id="kinetic_equations.C_3" name="C_3" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.C_2" name="C_2" public_interface="out" units="umol" />
<variable cmeta:id="kinetic_equations.C_1" name="C_1" public_interface="out" units="umol" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_1</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_21</ci>
<ci>C_2</ci>
</apply>
<apply>
<times />
<ci>k_61</ci>
<ci>C_6</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_12</ci>
<ci>k_16</ci>
</apply>
<ci>C_1</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_2</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_12</ci>
<ci>C_1</ci>
</apply>
<apply>
<times />
<ci>k_32</ci>
<ci>C_3</ci>
</apply>
<apply>
<times />
<ci>k_52</ci>
<ci>C_5</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_21</ci>
<ci>k_23</ci>
<ci>k_25</ci>
</apply>
<ci>C_2</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_3</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_23</ci>
<ci>C_2</ci>
</apply>
<apply>
<times />
<ci>k_43</ci>
<ci>C_4</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_32</ci>
<ci>k_34</ci>
</apply>
<ci>C_3</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_4</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_34</ci>
<ci>C_3</ci>
</apply>
<apply>
<times />
<ci>k_54</ci>
<ci>C_5</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_45</ci>
<ci>k_43</ci>
</apply>
<ci>C_4</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_5</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_45</ci>
<ci>C_4</ci>
</apply>
<apply>
<times />
<ci>k_65</ci>
<ci>C_6</ci>
</apply>
<apply>
<times />
<ci>k_25</ci>
<ci>C_2</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_54</ci>
<ci>k_52</ci>
<ci>k_56</ci>
</apply>
<ci>C_5</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>C_6_temp</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>k_16</ci>
<ci>C_1</ci>
</apply>
<apply>
<times />
<ci>k_56</ci>
<ci>C_5</ci>
</apply>
</apply>
<apply>
<times />
<apply>
<plus />
<ci>k_61</ci>
<ci>k_65</ci>
</apply>
<ci>C_6_temp</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>C_6</ci>
<apply>
<minus />
<ci>C_T</ci>
<apply>
<plus />
<ci>C_1</ci>
<ci>C_2</ci>
<ci>C_3</ci>
<ci>C_4</ci>
<ci>C_5</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="environment">
<variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
</component>
<component name="ion_concentrations">
<variable cmeta:id="ion_concentrations.glucose_i" name="glucose_i" public_interface="out" units="M" />
<variable cmeta:id="ion_concentrations.Na_o" name="Na_o" public_interface="out" units="M" />
<variable cmeta:id="ion_concentrations.V" name="V" public_interface="out" units="volt" />
<variable cmeta:id="ion_concentrations.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="ion_concentrations.glucose_o" name="glucose_o" public_interface="out" units="M" />
<variable cmeta:id="ion_concentrations.Na_i" name="Na_i" public_interface="out" units="M" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>V</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="volt_per_second">
100
<sep />
-6
</cn>
</apply>
</math>
</component>
<connection>
<map_components component_1="parameters" component_2="kinetic_equations" />
<map_variables variable_1="C_T" variable_2="C_T" />
</connection>
<connection>
<map_components component_1="king_altman_states" component_2="NBC_current" />
<map_variables variable_1="C4" variable_2="C4" />
<map_variables variable_1="C1" variable_2="C1" />
<map_variables variable_1="C2" variable_2="C2" />
<map_variables variable_1="C6" variable_2="C6" />
<map_variables variable_1="C5" variable_2="C5" />
<map_variables variable_1="C3" variable_2="C3" />
</connection>
<connection>
<map_components component_1="ion_concentrations" component_2="rate_constants" />
<map_variables variable_1="glucose_i" variable_2="glucose_i" />
<map_variables variable_1="Na_o" variable_2="Na_o" />
<map_variables variable_1="glucose_o" variable_2="glucose_o" />
<map_variables variable_1="Na_i" variable_2="Na_i" />
</connection>
<connection>
<map_components component_1="ion_concentrations" component_2="phenomonological_constants" />
<map_variables variable_1="Na_o" variable_2="Na_o" />
<map_variables variable_1="glucose_o" variable_2="glucose_o" />
</connection>
<connection>
<map_components component_1="rate_constants" component_2="king_altman_states" />
<map_variables variable_1="k_34" variable_2="k_34" />
<map_variables variable_1="k_23" variable_2="k_23" />
<map_variables variable_1="k_43" variable_2="k_43" />
<map_variables variable_1="k_16" variable_2="k_16" />
<map_variables variable_1="k_45" variable_2="k_45" />
<map_variables variable_1="k_25" variable_2="k_25" />
<map_variables variable_1="k_52" variable_2="k_52" />
<map_variables variable_1="k_61" variable_2="k_61" />
<map_variables variable_1="k_65" variable_2="k_65" />
<map_variables variable_1="k_12" variable_2="k_12" />
<map_variables variable_1="k_32" variable_2="k_32" />
<map_variables variable_1="k_54" variable_2="k_54" />
<map_variables variable_1="k_21" variable_2="k_21" />
<map_variables variable_1="k_56" variable_2="k_56" />
</connection>
<connection>
<map_components component_1="parameters" component_2="rate_constants" />
<map_variables variable_1="alpha_p" variable_2="alpha_p" />
<map_variables variable_1="k0_56" variable_2="k0_56" />
<map_variables variable_1="k0_12" variable_2="k0_12" />
<map_variables variable_1="k0_32" variable_2="k0_32" />
<map_variables variable_1="k0_52" variable_2="k0_52" />
<map_variables variable_1="z_c" variable_2="z_c" />
<map_variables variable_1="n" variable_2="n" />
<map_variables variable_1="k0_65" variable_2="k0_65" />
<map_variables variable_1="k0_16" variable_2="k0_16" />
<map_variables variable_1="k0_43" variable_2="k0_43" />
<map_variables variable_1="k0_54" variable_2="k0_54" />
<map_variables variable_1="delta" variable_2="delta" />
<map_variables variable_1="k0_25" variable_2="k0_25" />
<map_variables variable_1="k0_61" variable_2="k0_61" />
<map_variables variable_1="k0_45" variable_2="k0_45" />
<map_variables variable_1="k0_34" variable_2="k0_34" />
<map_variables variable_1="k0_21" variable_2="k0_21" />
<map_variables variable_1="z_Na" variable_2="z_Na" />
<map_variables variable_1="C_T" variable_2="C_T" />
<map_variables variable_1="k0_23" variable_2="k0_23" />
<map_variables variable_1="alpha_pp" variable_2="alpha_pp" />
<map_variables variable_1="mu" variable_2="mu" />
</connection>
<connection>
<map_components component_1="parameters" component_2="phenomonological_constants" />
<map_variables variable_1="C_T" variable_2="C_T" />
<map_variables variable_1="k0_23" variable_2="k0_23" />
<map_variables variable_1="F" variable_2="F" />
</connection>
<connection>
<map_components component_1="rate_constants" component_2="kinetic_equations" />
<map_variables variable_1="k_34" variable_2="k_34" />
<map_variables variable_1="k_23" variable_2="k_23" />
<map_variables variable_1="k_43" variable_2="k_43" />
<map_variables variable_1="k_16" variable_2="k_16" />
<map_variables variable_1="k_45" variable_2="k_45" />
<map_variables variable_1="k_25" variable_2="k_25" />
<map_variables variable_1="k_52" variable_2="k_52" />
<map_variables variable_1="k_61" variable_2="k_61" />
<map_variables variable_1="k_65" variable_2="k_65" />
<map_variables variable_1="k_12" variable_2="k_12" />
<map_variables variable_1="k_32" variable_2="k_32" />
<map_variables variable_1="k_54" variable_2="k_54" />
<map_variables variable_1="k_21" variable_2="k_21" />
<map_variables variable_1="k_56" variable_2="k_56" />
</connection>
<connection>
<map_components component_1="parameters" component_2="NBC_current" />
<map_variables variable_1="alpha_p" variable_2="alpha_p" />
<map_variables variable_1="delta" variable_2="delta" />
<map_variables variable_1="z_Na" variable_2="z_Na" />
<map_variables variable_1="z_c" variable_2="z_c" />
<map_variables variable_1="alpha_pp" variable_2="alpha_pp" />
<map_variables variable_1="n" variable_2="n" />
<map_variables variable_1="F" variable_2="F" />
</connection>
<connection>
<map_components component_1="rate_constants" component_2="phenomonological_constants" />
<map_variables variable_1="k_34" variable_2="k_34" />
<map_variables variable_1="k_23" variable_2="k_23" />
<map_variables variable_1="k_43" variable_2="k_43" />
<map_variables variable_1="ks_12" variable_2="ks_12" />
<map_variables variable_1="k_16" variable_2="k_16" />
<map_variables variable_1="k_45" variable_2="k_45" />
<map_variables variable_1="k_25" variable_2="k_25" />
<map_variables variable_1="k_52" variable_2="k_52" />
<map_variables variable_1="k_61" variable_2="k_61" />
<map_variables variable_1="k_65" variable_2="k_65" />
<map_variables variable_1="k_12" variable_2="k_12" />
<map_variables variable_1="k_32" variable_2="k_32" />
<map_variables variable_1="k_54" variable_2="k_54" />
<map_variables variable_1="k_21" variable_2="k_21" />
<map_variables variable_1="k_56" variable_2="k_56" />
</connection>
<connection>
<map_components component_1="kinetic_equations" component_2="NBC_current" />
<map_variables variable_1="C_3" variable_2="C_3" />
<map_variables variable_1="C_1" variable_2="C_1" />
<map_variables variable_1="C_6" variable_2="C_6" />
<map_variables variable_1="C_2" variable_2="C_2" />
<map_variables variable_1="C_5" variable_2="C_5" />
<map_variables variable_1="C_4" variable_2="C_4" />
</connection>
<connection>
<map_components component_1="environment" component_2="ion_concentrations" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="environment" component_2="kinetic_equations" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="ion_concentrations" component_2="parameters" />
<map_variables variable_1="V" variable_2="V" />
</connection>
<connection>
<map_components component_1="rate_constants" component_2="NBC_current" />
<map_variables variable_1="k_34" variable_2="k_34" />
<map_variables variable_1="k_52" variable_2="k_52" />
<map_variables variable_1="k_61" variable_2="k_61" />
<map_variables variable_1="k_65" variable_2="k_65" />
<map_variables variable_1="k_12" variable_2="k_12" />
<map_variables variable_1="k_43" variable_2="k_43" />
<map_variables variable_1="k_16" variable_2="k_16" />
<map_variables variable_1="k_21" variable_2="k_21" />
<map_variables variable_1="k_25" variable_2="k_25" />
<map_variables variable_1="k_56" variable_2="k_56" />
</connection>
<connection>
<map_components component_1="parameters" component_2="king_altman_states" />
<map_variables variable_1="C_T" variable_2="C_T" />
</connection>
</model>
