Integrated Model of Metabolism and Autoimmune Response in ß-Cell Death and Progression to Type 1 Diabetes

Tijana Marinković, Marko Sysi-Aho, Matej Orešič (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

7 Citations (Scopus)

Abstract

Progression to type 1 diabetes is characterized by complex interactions of environmental, metabolic and immune system factors, involving both degenerative pathways leading to loss of pancreatic β-cells as well as protective pathways. The interplay between the degenerative and protective pathways may hold the key to disease outcomes, but no models have so far captured the two together. Here we propose a mathematical framework, an ordinary differential equation (ODE) model, which integrates metabolism and the immune system in early stages of disease process. We hypothesize that depending on the degree of regulation, autoimmunity may also play a protective role in the initial response to stressors. We assume that β-cell destruction follows two paths of loss: degenerative and autoimmune-induced loss. The two paths are mutually competing, leading to termination of the degenerative loss and further to elimination of the stress signal and the autoimmune response, and ultimately stopping the β-cell loss. The model describes well our observations from clinical and non-clinical studies and allows exploration of how the rate of β-cell loss depends on the amplitude and duration of autoimmune response.
Original languageEnglish
Article number51909
JournalPLoS ONE
Volume7
Issue number12
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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autoimmunity
insulin-dependent diabetes mellitus
Cell death
Medical problems
Autoimmunity
Type 1 Diabetes Mellitus
Metabolism
cell death
Cell Death
metabolism
immune system
Immune System
Immune system
cells
Immunologic Factors
Ordinary differential equations
duration

Cite this

Marinković, Tijana ; Sysi-Aho, Marko ; Orešič, Matej. / Integrated Model of Metabolism and Autoimmune Response in ß-Cell Death and Progression to Type 1 Diabetes. In: PLoS ONE. 2012 ; Vol. 7, No. 12.
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Integrated Model of Metabolism and Autoimmune Response in ß-Cell Death and Progression to Type 1 Diabetes. / Marinković, Tijana; Sysi-Aho, Marko; Orešič, Matej (Corresponding Author).

In: PLoS ONE, Vol. 7, No. 12, 51909, 2012.

Research output: Contribution to journalArticleScientificpeer-review

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AB - Progression to type 1 diabetes is characterized by complex interactions of environmental, metabolic and immune system factors, involving both degenerative pathways leading to loss of pancreatic β-cells as well as protective pathways. The interplay between the degenerative and protective pathways may hold the key to disease outcomes, but no models have so far captured the two together. Here we propose a mathematical framework, an ordinary differential equation (ODE) model, which integrates metabolism and the immune system in early stages of disease process. We hypothesize that depending on the degree of regulation, autoimmunity may also play a protective role in the initial response to stressors. We assume that β-cell destruction follows two paths of loss: degenerative and autoimmune-induced loss. The two paths are mutually competing, leading to termination of the degenerative loss and further to elimination of the stress signal and the autoimmune response, and ultimately stopping the β-cell loss. The model describes well our observations from clinical and non-clinical studies and allows exploration of how the rate of β-cell loss depends on the amplitude and duration of autoimmune response.

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