The influence of oral insulin on the development of autoimmune diabetes in NOD mice fed a hypoallergenic diet.
BACKGROUND
Autoimmune diabetes can be prevented in animal models by hypoallergenic diets. Moreover, in animal models, oral administration of insulin can suppress the development of autoimmune diabetes and clinical trials on prevention of human Type 1 diabetes by oral administration of insulin are already taking place. However, it has been reported that autoimmune diabetes can be induced by oral administration of an auto-antigen (insulin), and great caution is therefore warranted when applying the oral tolerance approach to prevent Type 1 diabetes.


OBJECTIVE
To evaluate the effect of orally administered insulin on the development of autoimmune diabetes in non-obese diabetic mice fed a hypoallergenic diet.


METHODS
Four groups of mice were fed regular mouse chow (group 1, control mice), hypoallergenic diet, using the hydrolyzed infant formula Pregistimil (group 2), and Pregistimil with oral insulin (4 U/l of drinking water, group 3; and 8 U/l of drinking water, group 4).


RESULTS
At 210 days of age, 11/20 (55%) mice in group 1 developed diabetes. In contrast, none of the mice from the Pregistimil-fed groups (0/16, 0/14, 0/17) developed the disease (p<0.001). The incidence of infiltrated islets and the severity of insulitis, at age 90 days, was significantly lower in mice fed with the hypoallegenic diet than in controls (p=0.028).


CONCLUSIONS
In NOD mice fed a diet that prevents the development of diabetes, oral insulin supplementation appears to be safe, since it does not promote the development of clinical diabetes.
Shehadeh
N
N
Pediatric Diabetes Unit, Rambam Medical Center, Haifa, Israel. n_shehadeh@rambam.health.gov.il
Weis
R
R
Teninboum
G
G
Benderly
A
A
Etzioni
A
A
Shamir
R
R
D000284:Administration, Oral; D000818:Animals; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011492:Protein Hydrolysates / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation
D002364:Caseins; D007328:Insulin; D011492:Protein Hydrolysates; C097269:pregestimil