Calcium and Glycolysis Mediate Multiple Bursting Modes in Pancreatic Islets
Catherine
Lloyd
Auckland Bioengineering Institute, University of Auckland
Model Status
This model has been rebuilt and coded by translating the authors original XPPAUT.ode file, which can be found at http://www.math.fsu.edu/~bertram/software/islet/BJ_04a.ode. This file runs in PCEnv and COR and is able to produce the expected output. This model has been parameterised for the 'compound bursting' model. Some equations have inconsistent magnitudes due to the fact that time is defined in milliseconds, yet flux is defined in micromolar per second.
Model Structure
ABSTRACT: Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10-60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca2+ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic beta-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca2+ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call "glycolytic bursting." Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years.
Calcium and Glycolysis Mediate Multiple Bursting Modes in Pancreatic Islets, Richard Bertram, Leslie Satin, Min Zhang, Paul Smolen, and Arthur Sherman, 2004,
Biophysical Journal, 87, 3074-3087. PubMed ID: 15347584
cell diagram
A schematic diagram of the ionic currents and fluxes across the ER and the cell surface membranes which are described by the mathematical model.
calcium dynamics
insulin
glucose homeostasis
metabolism
James Lawson
James
Lawson
Richard
2004-11-01 00:00
Calcium and Glycolysis Mediate Multiple Bursting Modes in Pancreatic Islets (compound bursting model)
The University of Auckland, Auckland Bioengineering Institute
2007-08-06T12:07:27+12:00
1000
100000
0.01
bdf15
2007-08-03T00:00:00+00:00
Arthur
Sherman
James
Lawson
Richard
15347584
This is the CellML description of Bertram et al.'s 2004 mathematical model of calcium and glycolysis mediated bursting modes in pancreatic islets.
Catherine Lloyd
James
Lawson
Richard
2009-05-25T16:03:37+12:00
Calcium and Glycolysis Mediate Multiple Bursting Modes in Pancreatic Islets
87(5)
3074
3087
The University of Auckland
Auckland Bioengineering Institute
Leslie
Satin
This model has been rebuilt and coded by translating the authors original XPPAUT .ode file, which can be found at http://www.math.fsu.edu/~bertram/software/islet/BJ_04a.ode . This file runs in PCEnv and is able to produce the expected output for a few cycles, after which the output degenerates. This model has been parameterised for the 'compound bursting' model.
updated curation status
Biophysical Journal
Min
Zhang
Bertram et al.'s 2004 mathematical model of calcium and glycolysis mediated bursting modes in pancreatic islets.
Pancreatic Islets
Richard
Bertram
j.lawson@auckland.ac.nz
keyword
Paul
Smolen
The equation defining rgpdh has been changed from rgpdh = 0.2{units="dimensionless"} * root(fbp) to: rgpdh = 0.2{units="dimensionless"} * root(abs(fbp). Since rgpdh was starting to approach zero near where the offending NaN was being produced in version 01 variant 01. This partially fixes the problem but the output is still not totally satisfactory. The sqrt function in the equation defining rad also had an 'abs' function added: rad = root(abs(power(adp - atot, 2{units="dimensionless"}) - 4{units="dimensionless"} * power(adp, 2{units="dimensionless"}))