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

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...

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Main Authors:	Marinković, Tijana, Sysi-Aho, Marko, Orešič, Matej
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522595/

id	pubmed-3522595
recordtype	oai_dc
spelling	pubmed-35225952012-12-18 Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes Marinković, Tijana Sysi-Aho, Marko Orešič, Matej Research Article 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. Public Library of Science 2012-12-14 /pmc/articles/PMC3522595/ /pubmed/23251651 http://dx.doi.org/10.1371/journal.pone.0051909 Text en © 2012 Marinković et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Marinković, Tijana Sysi-Aho, Marko Orešič, Matej
spellingShingle	Marinković, Tijana Sysi-Aho, Marko Orešič, Matej Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
author_facet	Marinković, Tijana Sysi-Aho, Marko Orešič, Matej
author_sort	Marinković, Tijana
title	Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
title_short	Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
title_full	Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
title_fullStr	Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
title_full_unstemmed	Integrated Model of Metabolism and Autoimmune Response in β-Cell Death and Progression to Type 1 Diabetes
title_sort	integrated model of metabolism and autoimmune response in β-cell death and progression to type 1 diabetes
description	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.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522595/
_version_	1611940543953108992

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

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