Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration
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 secreti...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2424306 |
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| author | Susanne W. Bruun Knud Josefsen Julia T. Tanassi Aleš Marek Martin H. F. Pedersen Ulrik Sidenius Martin Haupt-Jorgensen Julie C. Antvorskov Jesper Larsen Niels H. Heegaard Karsten Buschard |
| author_facet | Susanne W. Bruun Knud Josefsen Julia T. Tanassi Aleš Marek Martin H. F. Pedersen Ulrik Sidenius Martin Haupt-Jorgensen Julie C. Antvorskov Jesper Larsen Niels H. Heegaard Karsten Buschard |
| author_sort | Susanne W. Bruun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fe19ad5d509b49ac928332016b8b7943 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-fe19ad5d509b49ac928332016b8b79432025-02-03T06:04:55ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/24243062424306Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral AdministrationSusanne W. Bruun0Knud Josefsen1Julia T. Tanassi2Aleš Marek3Martin H. F. Pedersen4Ulrik Sidenius5Martin Haupt-Jorgensen6Julie C. Antvorskov7Jesper Larsen8Niels H. Heegaard9Karsten Buschard10The Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkThe Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkClinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, DenmarkThe Hevesy Laboratory, DTU Nutech, Technical University of Denmark, Roskilde, DenmarkThe Hevesy Laboratory, DTU Nutech, Technical University of Denmark, Roskilde, DenmarkEnzyme Purification and Characterization, Novozymes A/S, Bagsværd, DenmarkThe Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkThe Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkThe Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkClinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, DenmarkThe Bartholin Institute, Rigshospitalet, Copenhagen N, DenmarkGluten 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.http://dx.doi.org/10.1155/2016/2424306 |
| spellingShingle | Susanne W. Bruun Knud Josefsen Julia T. Tanassi Aleš Marek Martin H. F. Pedersen Ulrik Sidenius Martin Haupt-Jorgensen Julie C. Antvorskov Jesper Larsen Niels H. Heegaard Karsten Buschard Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration Journal of Diabetes Research |
| title | Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration |
| title_full | Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration |
| title_fullStr | Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration |
| title_full_unstemmed | Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration |
| title_short | Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration |
| title_sort | large gliadin peptides detected in the pancreas of nod and healthy mice following oral administration |
| url | http://dx.doi.org/10.1155/2016/2424306 |
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