Enteropathy precedes type 1 diabetes in the BB rat

• Published in: Gut Vol. 53; no. 10; pp. 1437 - 1444
• Main Authors: Graham, S, Courtois, P, Malaisse, W J, Rozing, J, Scott, F W, Mowat, A Mc I
• 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: Animals; BB control rats; BB diabetes prone rats; BBc; BBdp; beta-Fructofuranosidase - metabolism; Biological and medical sciences; CCPR; CD4+ T cells; Celiac disease; crypt cell production rate; dendritic cell; Diabetes; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - etiology; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 1 - enzymology; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - pathology; Diet; Diet - adverse effects; enteropathy; Experiments; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gluten; hydrolysed casein; IEL; Intestinal Diseases - enzymology; Intestinal Diseases - etiology; Intestinal Diseases - pathology; Intestinal Mucosa - enzymology; intraepithelial lymphocytes; Jejunum - pathology; Laboratory animals; Lymphocytes; Male; Medical sciences; Pancreas; Pathogenesis; Prediabetic State - enzymology; Prediabetic State - etiology; Prediabetic State - pathology; Proteins; R&D; Rats; Rats, Inbred BB; Research & development; Rodents; Small Intestine; Studies; T1D; Thymus Gland - physiopathology; tissue transglutaminase; tTG; type 1 autoimmune diabetes; type 1 diabetes; wheat gluten; Endocrinopathy; Autoimmunity; Insulitis; Rat; Pathogenesis; Check; Autoimmune disease; Small intestine; Jejunum; Casein; Immunological investigation; Surgery; Peroxidase; Immunopathology; Immune response; Digestive system; Enzyme; Rodentia; Histology; Method; Protein; Feeding; Vertebrata; Anatomic pathology; Mammalia; Diet therapy; Peroxidases; Diet; Type 1 diabetes; Animal; Cereal; Models; Oxidoreductases
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2004.042481

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.