Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes

OBJECTIVE: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining β-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease. RESEARCH DESIGN AND METHODS: Usi...

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Autores principales: Alanentalo, Tomas, Hörnblad, Andreas, Mayans, Sofia, Karin Nilsson, Anna, Sharpe, James, Larefalk, Åsa, Ahlgren, Ulf, Holmberg, Dan
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889776/
https://www.ncbi.nlm.nih.gov/pubmed/20393145
http://dx.doi.org/10.2337/db09-1400
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author Alanentalo, Tomas
Hörnblad, Andreas
Mayans, Sofia
Karin Nilsson, Anna
Sharpe, James
Larefalk, Åsa
Ahlgren, Ulf
Holmberg, Dan
author_facet Alanentalo, Tomas
Hörnblad, Andreas
Mayans, Sofia
Karin Nilsson, Anna
Sharpe, James
Larefalk, Åsa
Ahlgren, Ulf
Holmberg, Dan
author_sort Alanentalo, Tomas
collection PubMed
description OBJECTIVE: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining β-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease. RESEARCH DESIGN AND METHODS: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the three-dimensional spatial development and progression of insulitis and β-cell destruction in pancreata from diabetes-prone NOD and non–diabetes-prone congenic NOD.H-2b mice between 3 and 16 weeks of age. RESULTS: Together with results showing the spatial dynamics of the insulitis process, we provide data of β-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression. CONCLUSIONS: Our data provide a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.
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spelling pubmed-28897762011-07-01 Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes Alanentalo, Tomas Hörnblad, Andreas Mayans, Sofia Karin Nilsson, Anna Sharpe, James Larefalk, Åsa Ahlgren, Ulf Holmberg, Dan Diabetes Pathophysiology OBJECTIVE: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining β-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease. RESEARCH DESIGN AND METHODS: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the three-dimensional spatial development and progression of insulitis and β-cell destruction in pancreata from diabetes-prone NOD and non–diabetes-prone congenic NOD.H-2b mice between 3 and 16 weeks of age. RESULTS: Together with results showing the spatial dynamics of the insulitis process, we provide data of β-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression. CONCLUSIONS: Our data provide a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes. American Diabetes Association 2010-07 2010-04-14 /pmc/articles/PMC2889776/ /pubmed/20393145 http://dx.doi.org/10.2337/db09-1400 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Pathophysiology
Alanentalo, Tomas
Hörnblad, Andreas
Mayans, Sofia
Karin Nilsson, Anna
Sharpe, James
Larefalk, Åsa
Ahlgren, Ulf
Holmberg, Dan
Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title_full Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title_fullStr Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title_full_unstemmed Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title_short Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
title_sort quantification and three-dimensional imaging of the insulitis-induced destruction of β-cells in murine type 1 diabetes
topic Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889776/
https://www.ncbi.nlm.nih.gov/pubmed/20393145
http://dx.doi.org/10.2337/db09-1400
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