دورية أكاديمية
Increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody-positive donors prior to type 1 diabetes onset
| العنوان: | Increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody-positive donors prior to type 1 diabetes onset |
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| المؤلفون: | Rodriguez-Calvo, Teresa, Zapardiel-Gonzalo, Jose, Amirian, Natalie, Castillo, Ericka, Lajevardi, Yasaman, Krogvold, Lars, Dahl-Jørgensen, Knut, Von Herrath, Matthias G. |
| المصدر: | 0012-1797. |
| بيانات النشر: | The American Diabetes Association |
| سنة النشر: | 2017 |
| المجموعة: | Universitet i Oslo: Digitale utgivelser ved UiO (DUO) |
| الوصف: | 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 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | ANDRE/National Institutes of Health Grant R01 AI092453-03; http://urn.nb.no/URN:NBN:no-65793Test; 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; http://hdl.handle.net/10852/63236Test; 1503137; 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; Diabetes; 66; 1334; 1345; http://dx.doi.org/10.2337/db16-1343Test; URN:NBN:no-65793; Fulltext https://www.duo.uio.no/bitstream/handle/10852/63236/2/Manuscript_Rodriguez-Calvo_R2%2BPROOF.pdfTest |
| DOI: | 10.2337/db16-1343 |
| الإتاحة: | https://doi.org/10.2337/db16-1343Test http://hdl.handle.net/10852/63236Test http://urn.nb.no/URN:NBN:no-65793Test |
| رقم الانضمام: | edsbas.818BAAF0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db16-1343 |
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