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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.

SUBMITTER: Bruun SW

PROVIDER: S-EPMC5067331 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.

Bruun Susanne W SW Josefsen Knud K Tanassi Julia T JT Marek Aleš A Pedersen Martin H F MH Sidenius Ulrik U Haupt-Jorgensen Martin M Antvorskov Julie C JC Larsen Jesper J Heegaard Niels H NH Buschard Karsten K

Journal of diabetes research 20161004

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 direc ...[more]

PMID: 27795959

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Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.

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Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.

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