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Diabetologia
Published in: Diabetologia 11/2015

01-11-2015 | Article

Mast cells infiltrate pancreatic islets in human type 1 diabetes

Authors: Luisa Martino, Matilde Masini, Marco Bugliani, Lorella Marselli, Mara Suleiman, Ugo Boggi, Tatiane C. Nogueira, Franco Filipponi, Margherita Occhipinti, Daniela Campani, Francesco Dotta, Farooq Syed, Decio L. Eizirik, Piero Marchetti, Vincenzo De Tata

Published in: Diabetologia | Issue 11/2015

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Abstract

Aims/hypothesis

Beta cell destruction in human type 1 diabetes occurs through the interplay of genetic and environmental factors, and is mediated by immune cell infiltration of pancreatic islets. In this study, we explored the role of mast cells as an additional agent in the pathogenesis of type 1 diabetes insulitis.

Methods

Pancreatic tissue from donors without diabetes and with type 1 and 2 diabetes was studied using different microscopy techniques to identify islet-infiltrating cells. The direct effects of histamine exposure on isolated human islets and INS-1E cells were assessed using cell-survival studies and molecular mechanisms.

Results

A larger number of mast cells were found to infiltrate pancreatic islets in samples from donors with type 1 diabetes, compared with those from donors without diabetes or with type 2 diabetes. Evidence of mast cell degranulation was observed, and the extent of the infiltration correlated with beta cell damage. Histamine, an amine that is found at high levels in mast cells, directly contributed to beta cell death in isolated human islets and INS-1E cells via a caspase-independent pathway.

Conclusions/interpretation

These findings suggest that mast cells might be responsible, at least in part, for immune-mediated beta cell alterations in human type 1 diabetes. If this is the case, inhibition of mast cell activation and degranulation might act to protect beta cells in individuals with type 1 diabetes.
Appendix
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Metadata
Title
Mast cells infiltrate pancreatic islets in human type 1 diabetes
Authors
Luisa Martino
Matilde Masini
Marco Bugliani
Lorella Marselli
Mara Suleiman
Ugo Boggi
Tatiane C. Nogueira
Franco Filipponi
Margherita Occhipinti
Daniela Campani
Francesco Dotta
Farooq Syed
Decio L. Eizirik
Piero Marchetti
Vincenzo De Tata
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 11/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3734-1

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