SMALL INTESTINE

Enteropathy precedes type 1 diabetes in the BB rat

S Graham¹, P Courtois², W J Malaisse², J Rozing³, F W Scott⁴, A Mc I Mowat¹

¹ Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow, UK
² Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium
³ Department of Cell Biology, Section Immunology, Faculty of Medical Sciences, University of Groningen, Groningen, the Netherlands
⁴ Molecular Medicine Program, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada

Correspondence to:
Correspondence to:
Professor A Mowat
Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK; a.m.mowat{at}clinmed.gla.ac.uk

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.

Abbreviations: T1D, type 1 autoimmune diabetes; BBc, BB control rats; BBdp, BB diabetes prone rats; tTG, tissue transglutaminase; WG, wheat gluten; HC, hydrolysed casein; CCPR, crypt cell production rate; IEL, intraepithelial lymphocytes; DC, dendritic cell

Keywords: type 1 diabetes; enteropathy; diet; CD4+ T cells

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller
Gut 2004 53: 1391. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Mojibian, M., Chakir, H., Lefebvre, D. E., Crookshank, J. A., Sonier, B., Keely, E., Scott, F. W. (2009). Diabetes-Specific HLA-DR-Restricted Proinflammatory T-Cell Response to Wheat Polypeptides in Tissue Transglutaminase Antibody-Negative Patients With Type 1 Diabetes. Diabetes 58: 1789-1796 [Abstract] [Full Text]  
• Hadjiyanni, I., Li, K. K., Drucker, D. J. (2009). Glucagon-Like Peptide-2 Reduces Intestinal Permeability But Does Not Modify the Onset of Type 1 Diabetes in the Nonobese Diabetic Mouse. Endocrinology 150: 592-599 [Abstract] [Full Text]  
• Vaarala, O., Atkinson, M. A., Neu, J. (2008). The "Perfect Storm" for Type 1 Diabetes: The Complex Interplay Between Intestinal Microbiota, Gut Permeability, and Mucosal Immunity. Diabetes 57: 2555-2562 [Abstract] [Full Text]  
• Geoffrey, R., Jia, S., Kwitek, A. E., Woodliff, J., Ghosh, S., Lernmark, A., Wang, X., Hessner, M. J. (2006). Evidence of a Functional Role for Mast Cells in the Development of Type 1 Diabetes Mellitus in the BioBreeding Rat. J. Immunol. 177: 7275-7286 [Abstract] [Full Text]  
• Dombrowski, F., Mathieu, C., Evert, M. (2006). Hepatocellular Neoplasms Induced by Low-Number Pancreatic Islet Transplants in Autoimmune Diabetic BB/Pfd Rats. Cancer Res. 66: 1833-1843 [Abstract] [Full Text]  
• Turley, S. J., Lee, J.-W., Dutton-Swain, N., Mathis, D., Benoist, C. (2005). Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc. Natl. Acad. Sci. USA 102: 17729-17733 [Abstract] [Full Text]