TY - JOUR
T1 - Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes
AU - Funda, David P
AU - Kaas, Anne
AU - Tlaskalová-Hogenová, Helena
AU - Buschard, Karsten
N1 - 2007 John Wiley & Sons, Ltd
PY - 2008
Y1 - 2008
N2 - BACKGROUND: Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice.METHODS: Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals.RESULTS: A significantly lower diabetes incidence (p < 0.0001) was observed in NOD mice fed gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p < 0.0001, 5.9%, n = 34). The minority of mice, which developed diabetes on all the three diabetes-protective (gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented.CONCLUSIONS: Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.
AB - BACKGROUND: Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice.METHODS: Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals.RESULTS: A significantly lower diabetes incidence (p < 0.0001) was observed in NOD mice fed gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p < 0.0001, 5.9%, n = 34). The minority of mice, which developed diabetes on all the three diabetes-protective (gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented.CONCLUSIONS: Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.
KW - Animals
KW - CD3 Complex/analysis
KW - Diabetes Mellitus, Type 1/immunology
KW - Diet
KW - Female
KW - Genetic Predisposition to Disease
KW - Glutens/administration & dosage
KW - Ileum/immunology
KW - Immunoglobulin A/metabolism
KW - Immunoglobulin M/metabolism
KW - Islets of Langerhans/pathology
KW - Jejunum/immunology
KW - Male
KW - Mice
KW - Mice, Inbred NOD
KW - Receptors, Antigen, T-Cell, gamma-delta/analysis
U2 - 10.1002/dmrr.748
DO - 10.1002/dmrr.748
M3 - Journal article
C2 - 17607660
SN - 1520-7552
VL - 24
SP - 59
EP - 63
JO - Diabetes - Metabolism: Research and Reviews
JF - Diabetes - Metabolism: Research and Reviews
IS - 1
ER -