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Integrated model of metabolism and autoimmune response in β-cell death and progression to type 1 diabetes
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.ORCID iD: 0000-0002-2856-9165
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, article id e51909Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 12, article id e51909
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-63674DOI: 10.1371/journal.pone.0051909ISI: 000312386800107PubMedID: 23251651Scopus ID: 2-s2.0-84871343233OAI: oai:DiVA.org:oru-63674DiVA, id: diva2:1169238
Note

Funding agencies:

Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) 250114 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-23Bibliographically approved

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Oresic, Matej

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CiteExportLink to record
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