title: Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes.
abstract: OBJECTIVE
  Type 1 diabetes is an autoimmune disorder that occurs in genetically susceptible individuals. It has been hypothesized that the disease could be triggered by environmental agents that gain entry into the body through small intestinal absorption. Increased intestinal permeability has been reported both in spontaneous animal models of type 1 diabetes and human type 1 diabetes. In these studies, we examined both the physical and functional permeability characteristics of the small intestine in diabetes-prone and control rats.
  
  
  METHODS
  In a series of studies, BioBreeding diabetes-prone(n = 31), BioBreeding diabetes-resistant (n = 20) and control Wistar (n = 25) rats were examined at intervals from 21 to 125 days of age.
  
  
  RESULTS
  The percentage of goblet cells and the mucosal crypt depth were significantly greater in BioBreeding diabetes-prone than BioBreeding diabetes-resistant rats (P < 0.001 and P = 0.01, respectively). BioBreeding diabetes-prone and BioBreeding diabetes-resistant rats expressed less of the tight junction protein claudin (P < 0.05) and exhibited greater intestinal permeability (P < 0.001) than did Wistar rats. Intestinal permeability measured both in vivo and ex vivo decreased in all rat strains as age increased (P < 0.001).
  
  
  CONCLUSIONS
  In a genetically susceptible rodent model of diabetes, early increased intestinal permeability might allow unregulated passage of environmental antigens that could potentially trigger the autoimmune response leading to type 1 diabetes.
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, Florida 32610, USA. neuj@peds.ufl.edu
authors.forename: Josef
authors.initials: J
authors.lastname: Neu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reverte
authors.forename: Amy D
authors.initials: AD
authors.lastname: Mackey
authors.forename: Kellym
authors.initials: K
authors.lastname: Liboni
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Tuhacek-Tenace
authors.forename: Marguerite
authors.initials: M
authors.lastname: Hatch
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Caicedo
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015153:Blotting, Western; D062445:Claudin-1; D003921:Diabetes Mellitus, Experimental / Q000209:etiology* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010539:Permeability; D011897:Random Allocation; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar
chemical_list: D001323:Autoantibodies; C568108:CLDN1 protein, human; D062445:Claudin-1; C568114:Cldn1 protein, rat; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat