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BIOMD0000000382 - Sturis1991_InsulinGlucoseModel_UltradianOscillation


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Reference Publication
Publication ID: 2035636
Sturis J, Polonsky KS, Mosekilde E, Van Cauter E.
Computer model for mechanisms underlying ultradian oscillations of insulin and glucose.
Am. J. Physiol. 1991 May; 260(5 Pt 1): E801-9
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.  [more]
Original Model: BIOMD0000000382.origin
Submitter: Ishan Ajmera
Submission ID: MODEL1110180000
Submission Date: 18 Oct 2011 10:28:38 UTC
Last Modification Date: 08 Apr 2016 17:10:20 UTC
Creation Date: 18 Oct 2011 10:36:35 UTC
Encoders:  Ishan Ajmera
set #1
bqbiol:hasProperty Human Disease Ontology diabetes mellitus
set #2
bqbiol:encodes Gene Ontology glucose import in response to insulin stimulus
Gene Ontology glucose transport
Gene Ontology insulin secretion
set #3
bqbiol:hasTaxon Taxonomy Homo sapiens

This a model from the article:
Computer model for mechanisms underlying ultradian oscillations of insulin and glucose.
Sturis J, Polonsky KS, Mosekilde E, Van Cauter E. Am J Physiol.1991 May;260(5 Pt 1):E801-9. 2035636,
Oscillations in human insulin secretion have been observed in two distinct period ranges, 10-15 min (i.e. rapid) and 100-150 min (i.e., ultradian). The cause of the ultradian oscillations remains to be elucidated. To determine whether the oscillations could result from the feedback loops between insulin and glucose, a parsimonious mathematical model including the major mechanisms involved in glucose regulation was developed. This model comprises two major negative feedback loops describing the effects of insulin on glucose utilization and glucose production, respectively, and both loops include the stimulatory effect of glucose on insulin secretion. Model formulations and parameters are representative of results from published clinical investigations. The occurrence of sustained insulin and glucose oscillations was found to be dependent on two essential features: 1) a time delay of 30-45 min for the effect of insulin on glucose production and 2) a sluggish effect of insulin on glucose utilization, because insulin acts from a compartment remote from plasma. When these characteristics were incorporated in the model, numerical simulations mimicked all experimental findings so far observed for these ultradian oscillations, including 1) self-sustained oscillations during constant glucose infusion at various rates; 2) damped oscillations after meal or oral glucose ingestion; 3) increased amplitude of oscillation after increased stimulation of insulin secretion, without change in frequency; and 4) slight advance of the glucose oscillation compared with the insulin oscillation.(ABSTRACT TRUNCATED AT 250 WORDS)

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The 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.

Publication ID: 2035636 Submission Date: 18 Oct 2011 10:28:38 UTC Last Modification Date: 08 Apr 2016 17:10:20 UTC Creation Date: 18 Oct 2011 10:36:35 UTC
Mathematical expressions
Rate Rule (variable: x) Rate Rule (variable: y) Rate Rule (variable: z) Rate Rule (variable: h1)
Rate Rule (variable: h2) Rate Rule (variable: h3) Assignment Rule (variable: f1) Assignment Rule (variable: f2)
Assignment Rule (variable: f3) Assignment Rule (variable: f5) Assignment Rule (variable: f4)  
Physical entities
Compartments Species
compartment1 x y z
h1 h2 h3
Global parameters
f1 f2 f3 f4
f5 v1 v2 v3
t1 t2 t3 I
Reactions (0)
Rules (11)
 Rate Rule (name: x) d [ x] / d t= f1-E*(x/v1-y/v2)-x/t1
 Rate Rule (name: y) d [ y] / d t= E*(x/v1-y/v2)-y/t2
 Rate Rule (name: z) d [ z] / d t= f5+I-f2-f3*f4
 Rate Rule (name: h1) d [ h1] / d t= 3*(x-h1)/t3
 Rate Rule (name: h2) d [ h2] / d t= 3*(h1-h2)/t3
 Rate Rule (name: h3) d [ h3] / d t= 3*(h2-h3)/t3
 Assignment Rule (name: f1) f1 = 209/(1+exp((-z)/(300*v3)+6.6))
 Assignment Rule (name: f2) f2 = 72*(1-exp((-z)/144*v3))
 Assignment Rule (name: f3) f3 = 0.01*z/v3
 Assignment Rule (name: f5) f5 = 180/(1+exp(0.29*h3/v1-7.5))
 Assignment Rule (name: f4) f4 = 90/(1+exp((-1.772)*log(y*(1/v2+1/(E*t2)))+7.76))+4
   compartment1 Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: compartment1
Initial amount: 90.0
Compartment: compartment1
Initial amount: 180.0
Compartment: compartment1
Initial amount: 13000.0
Compartment: compartment1
Initial amount: 70.0
Compartment: compartment1
Initial amount: 70.0
Compartment: compartment1
Initial amount: 70.0
Global Parameters (13)
Value: NaN
Value: NaN
Value: NaN
Value: NaN
Value: NaN
Value: 3.0
Value: 11.0
Value: 10.0
Value: 6.0
Value: 100.0
Value: 36.0
Value: 216.0
Value: 0.21
Representative curation result(s)
Representative curation result(s) of BIOMD0000000382

Curator's comment: (updated: 18 Oct 2011 11:36:23 BST)

Figure 5B of the reference publication has been reproduced here.In order to obtain figure 5B, the initial concentration of x,y,z and h species was taken as 90,180,13000 and 70 respectively.The model was integrated and simulated using Copasi v4.7(Build 34).