title: Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.
abstract: 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.
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Susanne W
authors: 0000-0002-7678-2681
authors: SW
authors: Bruun
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Knud
authors: 0000-0002-5093-2901
authors: K
authors: Josefsen
authors: Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, Denmark.
authors: Julia T
authors: 0000-0002-2921-8084
authors: JT
authors: Tanassi
authors: The Hevesy Laboratory, DTU Nutech, Technical University of Denmark, Roskilde, Denmark; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6, Czech Republic.
authors: Aleš
authors: 0000-0001-9031-8263
authors: A
authors: Marek
authors: The Hevesy Laboratory, DTU Nutech, Technical University of Denmark, Roskilde, Denmark.
authors: Martin H F
authors: 0000-0002-0719-4106
authors: MH
authors: Pedersen
authors: Enzyme Purification and Characterization, Novozymes A/S, Bagsværd, Denmark.
authors: Ulrik
authors: U
authors: Sidenius
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Martin
authors: 0000-0003-4088-5862
authors: M
authors: Haupt-Jorgensen
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Julie C
authors: 0000-0003-2618-6301
authors: JC
authors: Antvorskov
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Jesper
authors: 0000-0001-9317-9481
authors: J
authors: Larsen
authors: Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, Denmark.
authors: Niels H
authors: NH
authors: Heegaard
authors: The Bartholin Institute, Rigshospitalet, Copenhagen N, Denmark.
authors: Karsten
authors: 0000-0002-0126-7423
authors: K
authors: Buschard
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D005903:Gliadin / Q000276:immunology / Q000493:pharmacokinetics*; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D010539:Permeability; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D007328:Insulin; D010446:Peptide Fragments; D005903:Gliadin