S Brugman1, F A Klatter2, J Visser3, N A Bos2, D Elias4, J Rozing2. 1. 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. 2. Department of Cell Biology, Immunology Section, Groningen University, A. Deusinglaan 1, 11th Floor, Room 1121, 9713 AV, Groningen, The Netherlands. 3. Department of Medical Microbiology, Molecular Virology Section, Groningen University, The Netherlands. 4. Peptor, Rehovot, Israel.
Abstract
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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-DPrats 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/ INTERPRETATION: 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.
Authors: S Brugman; F A Klatter; J T J Visser; A C M Wildeboer-Veloo; H J M Harmsen; J Rozing; N A Bos Journal: Diabetologia Date: 2006-07-01 Impact factor: 10.122
Authors: J T J Visser; K Lammers; A Hoogendijk; M W Boer; S Brugman; S Beijer-Liefers; A Zandvoort; H Harmsen; G Welling; F Stellaard; N A Bos; A Fasano; J Rozing Journal: Diabetologia Date: 2010-09-19 Impact factor: 10.122
Authors: C H F Hansen; L Krych; D S Nielsen; F K Vogensen; L H Hansen; S J Sørensen; K Buschard; A K Hansen Journal: Diabetologia Date: 2012-05-10 Impact factor: 10.122
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