Enteropathy precedes type 1 diabetes in the BB rat
Background and aims: There is increasing evidence implicating intestinal immune responses to dietary proteins in the pathogenesis of type 1 autoimmune diabetes (T1D). Here we investigated the association between intestinal pathology and dietary factors in T1D by examining the mucosal architecture in...
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Published in | Gut Vol. 53; no. 10; pp. 1437 - 1444 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd and British Society of Gastroenterology
01.10.2004
BMJ BMJ Publishing Group LTD Copyright 2004 by Gut |
Subjects | |
Online Access | Get full text |
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Summary: | Background and aims: There is increasing evidence implicating intestinal immune responses to dietary proteins in the pathogenesis of type 1 autoimmune diabetes (T1D). Here we investigated the association between intestinal pathology and dietary factors in T1D by examining the mucosal architecture in the BB rat model. Methods: BB control (BBc) and diabetes prone (BBdp) rats were fed either a diabetes retardant hydrolysed casein based diet or one of two cereal based diets that promote the development of diabetes. Intestinal architecture was assessed in the jejunum by microdissection, histology, and immunohistology, and by measuring peroxidase activity and brush border invertase levels. Results: Enteropathy was present in BBdp rats soon after weaning, as assessed by increases in crypt length and in the proliferative activity of crypt epithelial cells in the jejunum, and this remained constant until 120 days of age. There was also a decrease in invertase activity, as well as increased numbers of intraepithelial lymphocytes, increased levels of mucosal peroxidase activity, and infiltration of the mucosa by CD4+ T lymphocytes. Equivalent enteropathy was present at all times in BBdp rats and was not influenced by the nature of the diet or by thymectomy at three weeks at age, procedures which prevent the development of diabetes. Conclusion: Enteropathy is a consistent feature in the diabetes prone BB rat but it precedes the onset of insulitis and appears to be due to mechanisms distinct from those which cause diabetes. The beneficial effects of the diabetes retardant hydrolysed casein diet on diabetes are not due to an effect on intestinal architecture per se but mucosal damage may be necessary for the development of autoreactivity in the pancreas. |
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Bibliography: | ark:/67375/NVC-75P4HMTK-Q Correspondence to: Professor A Mowat Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK; a.m.mowat@clinmed.gla.ac.uk PMID:15361491 local:0531437 istex:0CF9BBB953998DD2660B67F855B67B1CC46D13C5 href:gutjnl-53-1437.pdf ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Correspondence to: Professor A Mowat Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK; a.m.mowat@clinmed.gla.ac.uk |
ISSN: | 0017-5749 1468-3288 1458-3288 |
DOI: | 10.1136/gut.2004.042481 |