Cargando…
Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset
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 autoant...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399615/ https://www.ncbi.nlm.nih.gov/pubmed/28137793 http://dx.doi.org/10.2337/db16-1343 |
_version_ | 1783230676947959808 |
---|---|
author | Rodriguez-Calvo, Teresa Zapardiel-Gonzalo, Jose Amirian, Natalie Castillo, Ericka Lajevardi, Yasaman Krogvold, Lars Dahl-Jørgensen, Knut von Herrath, Matthias G. |
author_facet | Rodriguez-Calvo, Teresa Zapardiel-Gonzalo, Jose Amirian, Natalie Castillo, Ericka Lajevardi, Yasaman Krogvold, Lars Dahl-Jørgensen, Knut von Herrath, Matthias G. |
author_sort | Rodriguez-Calvo, Teresa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5399615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-53996152018-05-01 Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset Rodriguez-Calvo, Teresa Zapardiel-Gonzalo, Jose Amirian, Natalie Castillo, Ericka Lajevardi, Yasaman Krogvold, Lars Dahl-Jørgensen, Knut von Herrath, Matthias G. Diabetes Pathophysiology 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. American Diabetes Association 2017-05 2017-01-30 /pmc/articles/PMC5399615/ /pubmed/28137793 http://dx.doi.org/10.2337/db16-1343 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. |
spellingShingle | Pathophysiology 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 |
title | Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset |
title_full | Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset |
title_fullStr | Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset |
title_full_unstemmed | Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset |
title_short | Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset |
title_sort | increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody-positive donors prior to type 1 diabetes onset |
topic | Pathophysiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399615/ https://www.ncbi.nlm.nih.gov/pubmed/28137793 http://dx.doi.org/10.2337/db16-1343 |
work_keys_str_mv | AT rodriguezcalvoteresa increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT zapardielgonzalojose increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT amiriannatalie increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT castilloericka increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT lajevardiyasaman increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT krogvoldlars increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT dahljørgensenknut increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset AT vonherrathmatthiasg increaseinpancreaticproinsulinandpreservationofbcellmassinautoantibodypositivedonorspriortotype1diabetesonset |