Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes.
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.
Neu
Josef
J
Department of Pediatrics, University of Florida, Gainesville, Florida 32610, USA. neuj@peds.ufl.edu
Reverte
Christopher M
CM
Mackey
Amy D
AD
Liboni
Kellym
K
Tuhacek-Tenace
Lauren M
LM
Hatch
Marguerite
M
Li
Nan
N
Caicedo
Ricardo A
RA
Schatz
Desmond A
DA
Atkinson
Mark
M
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
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