dc.date.accessioned | 2018-08-20T11:39:07Z | |
dc.date.available | 2018-08-20T11:39:07Z | |
dc.date.created | 2017-10-08T16:41:13Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Rodriguez-Calvo, Teresa Zapardiel-Gonzalo, Jose Amirian, Natalie Castillo, Ericka Lajevardi, Yasaman Krogvold, Lars Dahl-Jørgensen, Knut Von Herrath, Matthias G. . Increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody-positive donors prior to type 1 diabetes onset. Diabetes. 2017, 66(5), 1334-1345 | |
dc.identifier.uri | http://hdl.handle.net/10852/63236 | |
dc.description.abstract | Type 1 diabetes is characterized by the loss of insulin production caused by β-cell dysfunction and/or destruction. The hypothesis that β-cell loss occurs early during the prediabetic phase has recently been challenged. Here we show, for the first time in situ, that in pancreas sections from autoantibody-positive (Ab+) donors, insulin area and β-cell mass are maintained before disease onset and that production of proinsulin increases. This suggests that β-cell destruction occurs more precipitously than previously assumed. Indeed, the pancreatic proinsulin-to-insulin area ratio was also increased in these donors with prediabetes. Using high-resolution confocal microscopy, we found a high accumulation of vesicles containing proinsulin in β-cells from Ab+ donors, suggesting a defect in proinsulin conversion or an accumulation of immature vesicles caused by an increase in insulin demand and/or a dysfunction in vesicular trafficking. In addition, islets from Ab+ donors were larger and contained a higher number of β-cells per islet. Our data indicate that β-cell mass (and function) is maintained until shortly before diagnosis and declines rapidly at the time of clinical onset of disease. This suggests that secondary prevention before onset, when β-cell mass is still intact, could be a successful therapeutic strategy.
© 2017 American Diabetes Association | en_US |
dc.language | EN | |
dc.publisher | The American Diabetes Association | |
dc.title | Increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody-positive donors prior to type 1 diabetes onset | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Rodriguez-Calvo, Teresa | |
dc.creator.author | Zapardiel-Gonzalo, Jose | |
dc.creator.author | Amirian, Natalie | |
dc.creator.author | Castillo, Ericka | |
dc.creator.author | Lajevardi, Yasaman | |
dc.creator.author | Krogvold, Lars | |
dc.creator.author | Dahl-Jørgensen, Knut | |
dc.creator.author | Von Herrath, Matthias G. | |
cristin.unitcode | 185,16,17,56 | |
cristin.unitname | Avdeling for pedodonti og atferdsfag | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1503137 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Diabetes&rft.volume=66&rft.spage=1334&rft.date=2017 | |
dc.identifier.jtitle | Diabetes | |
dc.identifier.volume | 66 | |
dc.identifier.issue | 5 | |
dc.identifier.startpage | 1334 | |
dc.identifier.endpage | 1345 | |
dc.identifier.doi | http://dx.doi.org/10.2337/db16-1343 | |
dc.identifier.urn | URN:NBN:no-65793 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0012-1797 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/63236/2/Manuscript_Rodriguez-Calvo_R2%2BPROOF.pdf | |
dc.type.version | AcceptedVersion | |
dc.relation.project | ANDRE/National Institutes of Health Grant R01 AI092453-03 | |