A stochastic mathematical model to study the autoimmune progression towards type 1 diabetes
Article first published online: 11 MAR 2013
Copyright © 2012 John Wiley & Sons, Ltd.
Diabetes/Metabolism Research and Reviews
Volume 29, Issue 3, pages 194–203, March 2013
How to Cite
Portuesi, R., Cherubini, C., Gizzi, A., Buzzetti, R., Pozzilli, P. and Filippi, S. (2013), A stochastic mathematical model to study the autoimmune progression towards type 1 diabetes. Diabetes Metab. Res. Rev., 29: 194–203. doi: 10.1002/dmrr.2382
- Issue published online: 11 MAR 2013
- Article first published online: 11 MAR 2013
- Accepted manuscript online: 10 DEC 2012 06:33PM EST
- Manuscript Accepted: 30 NOV 2012
- Manuscript Revised: 19 NOV 2012
- Manuscript Received: 30 MAR 2012
- type 1 diabetes;
- islet cells;
- beta cells;
- mathematical modelling;
- calcium oscillations;
The integrity of the interactions and the 3D architecture among beta cell populations in pancreatic islets is critical for proper biosynthesis, storage and release of insulin. The aim of this study was to evaluate the effect on electrophysiological signalling of beta cells that is produced by progressive lymphocytic islet cell infiltration (insulitis), by modelling the disruption of pancreatic islet anatomy as a consequence of insulitis and altered glucose concentrations.
On the basis of histopathological images of murine islets from non-obese diabetic mice, we simulated the electrophysiological dynamics of a 3D cluster of mouse beta cells via a stochastic model. Progressive damage was modelled at different glucose concentrations, representing the different glycaemic states in the autoimmune progression towards type 1 diabetes.
At 31% of dead beta cells (normoglycaemia) and 69% (hyperglycaemia), the system appeared to be biologically robust to maintain regular Ca2+ ion oscillations guaranteeing an effective insulin release. Simulations at 84%, 94% and 98% grades (severe hyperglycemia) showed that intracellular calcium oscillations were absent. In such conditions, insulin pulsatility is not expected to occur.
Our results suggest that the islet tissue is biophysically robust enough to compensate for high rates of beta cell loss. These predictions can be experimentally tested in vitro by quantifying space and time electrophysiological dynamics of animal islets kept at different glucose gradients. The model indicates the necessity of maintaining glycaemia within the physiological range as soon as possible after diabetes onset to avoid a dramatic interruption of Ca2+ pulsatility and the consequent drop of insulin release. Copyright © 2012 John Wiley & Sons, Ltd.