• Klíčová slova
• NOD mouse, beta-cell stress, enterovirus, environmental factors, gluten-free diet, gut-pancreas axis, intestinal permeability, type 1 diabetes,
• MeSH
• břicho MeSH
• diabetes mellitus 1. typu * MeSH
• lidé MeSH
• pankreas MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH

Type 1 diabetes (T1D) is an autoimmune disease with rising incidence. Pre- and manifest T1D is associated with intestinal barrier dysfunction, skewed microbiota composition, and serum dyslipidemia. The intestinal mucus layer protects against pathogens and its structure and phosphatidylcholine (PC) lipid composition may be compromised in T1D, potentially contributing to barrier dysfunction. This study compared prediabetic Non-Obese Diabetic (NOD) mice to healthy C57BL/6 mice by analyzing the intestinal mucus PC profile by shotgun lipidomics, plasma metabolomics by mass spectrometry and nuclear magnetic resonance, intestinal mucus production by histology, and cecal microbiota composition by 16 S rRNA sequencing. Jejunal mucus PC class levels were decreased in early prediabetic NOD vs C57BL/6 mice. In colonic mucus of NOD mice, the level of several PC species was reduced throughout prediabetes. In plasma, similar reductions of PC species were observed in early prediabetic NOD mice, where also increased beta-oxidation was prominent. No histological alterations were found in jejunal nor colonic mucus between the mouse strains. However, the β-diversity of the cecal microbiota composition differed between prediabetic NOD and C57BL/6 mice, and the bacterial species driving this difference were related to decreased short-chain fatty acid (SCFA)-production in the NOD mice. This study reports reduced levels of PCs in the intestinal mucus layer and plasma of prediabetic NOD mice as well as reduced proportions of SCFA-producing bacteria in cecal content at early prediabetes, possibly contributing to intestinal barrier dysfunction and T1D.

• Klíčová slova
• SCFA, Type 1 diabetes, metabolome, mucus lipids, phosphatidylcholine,
• MeSH
• diabetes mellitus 1. typu * MeSH
• fosfatidylcholiny MeSH
• hlen MeSH
• myši inbrední C57BL MeSH
• myši inbrední NOD MeSH
• myši MeSH
• prediabetes * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylcholiny MeSH

[This corrects the article DOI: 10.1155/2016/2424306.].

• Publikační typ
• tisková chyba MeSH

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   metabolismus   MeSH
• chromatografie kapalinová MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• gliadin imunologie   farmakokinetika   MeSH
• hmotnostní spektrometrie MeSH
• inzulin metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši inbrední NOD MeSH
• pankreas exokrinní metabolismus   MeSH
• pankreas metabolismus   MeSH
• peptidové fragmenty farmakokinetika   MeSH
• permeabilita MeSH
• sekrece inzulinu MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• střevní sliznice metabolismus   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gliadin MeSH
• inzulin MeSH
• peptidové fragmenty 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
• střevní sliznice 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
• Názvy látek
• jaderné receptory - podrodina 1, skupina F, člen 3 MeSH
• messenger RNA MeSH
• transkripční faktory TCF MeSH