Neonatal oral administration of DiaPep277, combined with hydrolysed casein diet, protects against Type 1 diabetes in BB-DP rats. An experimental study.
OBJECTIVE
Environmental factors such as diet and bacterial antigens play an important role in the onset of Type 1 diabetes. Different self-antigens are suggested to play a role in the development of diabetes. Antibodies against the 60-kDa heat shock protein 60, which have a high homology to bacterial heat shock protein 65, have been found in the circulation at the onset of diabetes in humans and in pre-diabetic NOD-mice. One of the immunodominant epitopes in autoimmune diabetes is p277, a specific peptide of human heat shock protein 60 corresponding to positions 437-460. In this study we investigated whether neonatal oral administration of DiaPep277 (a synthetic peptide analogue of p277) affected the development of diabetes in the BioBreeding-Diabetes Prone (BB-DP) rat, and whether this could potentiate the effect of a protective hydrolysed casein-diet.


METHODS
BB-DP rats were orally inoculated once per day with placebo or DiaPep277 at days 4, 5, 6 and 7 of life. At the age of 21 days rats were weaned on to a conventional, cereal-based diet or on to the hydrolysed casein-diet.


RESULTS
The development of diabetes in animals receiving DiaPep277 in combination with the hydrolysed casein-diet was delayed by 17 days, and a relative reduction of the incidence by 64% was seen. Non-diabetic animals did not show any sign of insulitis.


CONCLUSIONS
Short-term neonatal feeding with p277 in early life, combined with diet adaptation, appears to provide a procedure to significantly reduce the development of Type 1 diabetes in later life.
Brugman
S
S
Department of Cell Biology, Immunology Section, Groningen University, A. Deusinglaan 1, 11th Floor, Room 1121, 9713 AV, Groningen, The Netherlands. s.brugman@med.rug.nl.
Klatter
F A
FA
Department of Cell Biology, Immunology Section, Groningen University, A. Deusinglaan 1, 11th Floor, Room 1121, 9713 AV, Groningen, The Netherlands.
Visser
J
J
Department of Medical Microbiology, Molecular Virology Section, Groningen University, The Netherlands.
Bos
N A
NA
Department of Cell Biology, Immunology Section, Groningen University, A. Deusinglaan 1, 11th Floor, Room 1121, 9713 AV, Groningen, The Netherlands.
Elias
D
D
Peptor, Rehovot, Israel.
Rozing
J
J
Department of Cell Biology, Immunology Section, Groningen University, A. Deusinglaan 1, 11th Floor, Room 1121, 9713 AV, Groningen, The Netherlands.
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D018834:Chaperonin 60; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011913:Rats, Inbred BB
D018834:Chaperonin 60; C447781:DiaPep 277; D010446:Peptide Fragments; D010455:Peptides