BioModels Database logo

BioModels Database

spacer

BIOMD0000000381 - Maree2006_DuCa_Type1DiabetesModel

 

 |   |   |  Send feedback
Reference Publication
Publication ID: 16608707
Marée AF, Kublik R, Finegood DT, Edelstein-Keshet L.
Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease?
Philos Trans A Math Phys Eng Sci 2006 May; 364(1842): 1267-1282
Theoretical Biology/Bioinformatics, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. a.f.m.maree@bio.uu.nl  [more]
Model
Original Model: BIOMD0000000381.origin
Submitter: Ishan Ajmera
Submission ID: MODEL1110070000
Submission Date: 07 Oct 2011 16:34:06 UTC
Last Modification Date: 10 Oct 2014 11:36:07 UTC
Creation Date: 07 Oct 2011 16:36:41 UTC
Encoders:  Ishan Ajmera
set #1
bqbiol:isVersionOf Gene Ontology macrophage activation
Gene Ontology phagocytosis
Gene Ontology macrophage apoptotic process
set #2
bqbiol:isVersionOf Human Disease Ontology type 1 diabetes mellitus
set #3
bqbiol:hasTaxon Taxonomy Mus musculus
set #4
bqmodel:isDerivedFrom PubMed 10480594
Notes

This a model from the article:
Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease?
Maree AF, Kublik R, Finegood DT, Edelstein-Keshet L.Philos Transact A Math Phys Eng Sci.2006 May 15;364(1842):1267-82. 16608707,
Abstract:
A wave of apoptosis (programmed cell death) occurs normally in pancreatic beta-cells of newborn mice. We previously showed that macrophages from non-obese diabetic (NOD) mice become activated more slowly and engulf apoptotic cells at a lower rate than macrophages from control (Balb/c) mice. It has been hypothesized that this low clearance could result in secondary necrosis, escalating inflammation and self-antigen presentation that later triggers autoimmune, Type 1 diabetes (T1D). We here investigate whether this hypothesis could offer a reasonable and parsimonious explanation for onset of T1D in NOD mice. We quantify variants of the Copenhagen model (Freiesleben De Blasio et al. 1999 Diabetes 48, 1677), based on parameters from NOD and Balb/c experimental data. We show that the original Copenhagen model fails to explain observed phenomena within a reasonable range of parameter values, predicting an unrealistic all-or-none disease occurrence for both strains. However, if we take into account that, in general, activated macrophages produce harmful cytokines only when engulfing necrotic (but not apoptotic) cells, then the revised model becomes qualitatively and quantitatively reasonable. Further, we show that known differences between NOD and Balb/c mouse macrophage kinetics are large enough to account for the fact that an apoptotic wave can trigger escalating inflammatory response in NOD, but not Balb/c mice. In Balb/c mice, macrophages clear the apoptotic wave so efficiently, that chronic inflammation is prevented.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 16608707 Submission Date: 07 Oct 2011 16:34:06 UTC Last Modification Date: 10 Oct 2014 11:36:07 UTC Creation Date: 07 Oct 2011 16:36:41 UTC
Mathematical expressions
Rules
Assignment Rule (variable: x) Assignment Rule (variable: W) Rate Rule (variable: M) Rate Rule (variable: Ma)
Rate Rule (variable: Bn) Rate Rule (variable: Ba) Rate Rule (variable: Cy)  
Physical entities
Compartments Species
compartment1 M Ma Bn
Ba Cy  
Global parameters
J c b d
k e1 e2 Amax
kc alpha delta g
f1 f2 Wmax W
x      
Reactions (0)
Rules (7)
 
 Assignment Rule (name: parameter_1) x = ((time-9)/3)^2
 
 Assignment Rule (name: W) W = Wmax*exp(-parameter_1)
 
 Rate Rule (name: M) d [ M] / d t= J+(k+b)*Ma-c*M-f1*M*Ba-e1*M*(M+Ma)
 
 Rate Rule (name: Ma) d [ Ma] / d t= f1*M*Ba-k*Ma-e2*Ma*(M+Ma)
 
 Rate Rule (name: Bn) d [ Bn] / d t= d*Ba-(f1*M+f2*Ma)*Bn
 
 Rate Rule (name: Ba) d [ Ba] / d t= W+Amax*Cy/(kc+Cy)-(f1*M+f2*Ma+d)*Ba
 
 Rate Rule (name: Cy) d [ Cy] / d t= alpha*Bn*Ma-delta*Cy
 
   compartment1 Spatial dimensions: 3.0  Compartment size: 1.0
 
 M
Compartment: compartment1
Initial concentration: 477000.0
 
 Ma
Compartment: compartment1
Initial concentration: 0.0
 
 Bn
Compartment: compartment1
Initial concentration: 0.0
 
 Ba
Compartment: compartment1
Initial concentration: 0.0
 
   Cy
Compartment: compartment1
Initial concentration: 0.0
 
Global Parameters (17)
 
 J
Value: 50000.0
Constant
 
 c
Value: 0.1
Constant
 
 b
Value: 0.09
Constant
 
 d
Value: 0.5
Constant
 
 k
Value: 0.4
Constant
 
 e1
Value: 1.0E-8
Constant
 
 e2
Value: 1.0E-8
Constant
 
 Amax
Value: 2.0E7
Constant
 
 kc
Value: 1.0
Constant
 
 alpha
Value: 5.0E-9
Constant
 
 delta
Value: 25.0
Constant
 
 g
Value: 1.0E-5
Constant
 
 f1
Value: 1.0E-5
Constant
 
 f2
Value: 1.0E-5
Constant
 
 Wmax
Value: 4.0E7
Constant
 
  W
Value: 4936.39216346718
 
  x
Value: 9.0
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000381

Curator's comment: (updated: 07 Oct 2011 16:36:31 GMT)

The model reproduces fig 3 of the reference publication.
The model was integrated and simulated using Copasi v4.7 (Build 34).

spacer
spacer