[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
3-Hydroxycyclopent-1-ene-1-carboxylic acid (HOCPCA (1)) is a potent ligand for high-affinity γ-hydroxybutyric acid binding sites in the central nervous system. Various approaches to the introduction of a hydrogen label onto the HOCPCA skeleton are reported. The outcomes of the feasible C─H activation of olefin carbon (C-2) by iridium catalyst are compared with the reduction of the carbonyl group (C-3) by freshly prepared borodeuterides. The most efficient iridium catalysts proved to be Kerr bulky phosphine N-heterocyclic species providing outstanding deuterium enrichment (up to 91%) in a short period of time. The highest deuterium enrichment (>99%) was achieved through the reduction of ketone precursor 2 by lithium trimethoxyborodeuteride. Hence, analogical conditions were used for the tritiation experiment. [3 H]-HOCPCA selectively labeled on the position C-3 was synthetized with radiochemical purity >99%, an isolated yield of 637 mCi and specific activity = 28.9 Ci/mmol.
- Klíčová slova
- C─H activation, borotritides, hydrogen/deuterium exchange, iridium catalyst, tritium-labeled γ-hydroxybutyric acid,
- MeSH
- alkeny chemie MeSH
- bor chemie MeSH
- deuterium chemie MeSH
- hydroxybutyráty chemie MeSH
- iridium chemie MeSH
- izotopové značení MeSH
- katalýza MeSH
- ligandy MeSH
- oxidace-redukce MeSH
- tritium chemie MeSH
- vodík-deuteriová výměna * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 4-hydroxybutyric acid MeSH Prohlížeč
- alkeny MeSH
- bor MeSH
- deuterium MeSH
- hydroxybutyráty MeSH
- iridium MeSH
- ligandy MeSH
- tritium MeSH
