Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes.
- MeSH
- aplikace orální MeSH
- beta-buňky imunologie sekrece MeSH
- chromatografie kapalinová MeSH
- diabetes mellitus 1. typu imunologie MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- gliadin imunologie farmakokinetika MeSH
- hmotnostní spektrometrie MeSH
- inzulin sekrece MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši inbrední NOD MeSH
- pankreas exokrinní metabolismus sekrece MeSH
- pankreas metabolismus sekrece MeSH
- peptidové fragmenty farmakokinetika MeSH
- permeabilita MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- střeva metabolismus MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten. Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring. Methods. Nonobese diabetic mice were divided into 7 groups to receive combinations of gluten-free and standard diet before, during, or after pregnancy. Diabetes incidence in offspring was followed in each group (n = 16-27) for 310 days. Insulitis score and intestinal expression of T-cell transcription factors (RT-QPCR) were evaluated in animals from the different diet groups. Results. If mothers were fed a gluten-free diet only during pregnancy, the development of autoimmune diabetes in offspring was almost completely prevented with an incidence reduction from 62.5% in gluten-consuming mice to 8.3% (p < 0.0001) in the gluten-free group. The islets of Langerhans were less infiltrated (p < 0.001) and the intestinal expression of RORγt (Th17) (p < 0.0001) reduced in mice whose mothers were Gluten-free during pregnancy. Conclusion. A gluten-free diet exclusively during pregnancy efficiently prevents autoimmune diabetes development in offspring and reduces insulitis and intestinal expression of RORγt (Th17).
- MeSH
- bezlepková dieta metody MeSH
- diabetes mellitus 1. typu dietoterapie imunologie prevence a kontrola MeSH
- jaderné receptory - podrodina 1, skupina F, člen 3 genetika MeSH
- Langerhansovy ostrůvky imunologie patologie MeSH
- messenger RNA metabolismus MeSH
- myši inbrední NOD MeSH
- myši MeSH
- pankreatitida imunologie patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- střeva metabolismus MeSH
- těhotenství při diabetu dietoterapie MeSH
- těhotenství MeSH
- transkripční faktory TCF genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH