Document Detail

On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response.
MedLine Citation:
PMID:  22944599     Owner:  NLM     Status:  MEDLINE    
The cause of type 1 diabetes (T1D) remains unknown; however, a decisive role for environmental factors is recognized. The increased incidence of T1D during the last decades, as well as regional differences, is paralleled by differences in the intestinal bacterial flora. A new animal model was established to test the hypothesis that bacteria entering the pancreatic ductal system could trigger β-cell destruction and to provide new insights to the immunopathology of the disease. Obtained findings were compared with those present in two patients dying at onset of T1D. Different bacterial species, present in the human duodenum, instilled into the ductal system of the pancreas in healthy rats rapidly induced cellular infiltration, consisting of mainly neutrophil polymorphonuclear cells and monocytes/macrophages, centered around the pancreatic ducts. Also, the islets of Langerhans attracted polymorphonuclear cells, possibly via release of IL-6, IL-8, and monocyte chemotactic protein 1. Small bleedings or large dilatations of the capillaries were frequently found within the islets, and several β-cells had severe hydropic degeneration (ie, swollen cytoplasm) but with preserved nuclei. A novel rat model for the initial events in T1D is presented, revealing marked similarities with the morphologic findings obtained in patients dying at onset of T1D and signifying a decisive role for bacteria in eliciting an adverse innate immunity response. The present findings support the hypothesis that T1D is an organ-specific inflammatory disease.
Stella Korsgren; Ylva Molin; Kaija Salmela; Torbjörn Lundgren; Asa Melhus; Olle Korsgren
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-01
Journal Detail:
Title:  The American journal of pathology     Volume:  181     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-03-21     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1735-48     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Sweden.
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MeSH Terms
Bacteria / immunology*
Cytokines / secretion
Diabetes Mellitus, Type 1 / immunology*,  microbiology*,  pathology,  physiopathology
Disease Models, Animal
Fatal Outcome
Immunity, Innate / immunology*
Inflammation / complications,  immunology,  pathology
Islets of Langerhans / immunology,  microbiology,  pathology,  physiopathology
Models, Biological
Rats, Wistar
Grant Support
2U01AI065192-06/AI/NIAID NIH HHS
Reg. No./Substance:

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