Cargando…

Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells

Some report that adult human β-cells do not replicate, but we postulate this assumption is erroneous due a postmortem decline in replication markers such as Ki67. Our earlier report showed that Ki67-marked β-cells were rarely found in human cadaveric pancreases but were in the range of 0.2–0.5% in h...

Descripción completa

Detalles Bibliográficos
Autores principales: Sullivan, Brooke A., Hollister-Lock, Jennifer, Bonner-Weir, Susan, Weir, Gordon C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407864/
https://www.ncbi.nlm.nih.gov/pubmed/25488899
http://dx.doi.org/10.2337/db14-1675
_version_ 1782367971854778368
author Sullivan, Brooke A.
Hollister-Lock, Jennifer
Bonner-Weir, Susan
Weir, Gordon C.
author_facet Sullivan, Brooke A.
Hollister-Lock, Jennifer
Bonner-Weir, Susan
Weir, Gordon C.
author_sort Sullivan, Brooke A.
collection PubMed
description Some report that adult human β-cells do not replicate, but we postulate this assumption is erroneous due a postmortem decline in replication markers such as Ki67. Our earlier report showed that Ki67-marked β-cells were rarely found in human cadaveric pancreases but were in the range of 0.2–0.5% in human islets transplanted into mice. This study subjected 4-week-old mice to autopsy conditions that typically occur with humans. Mice were killed, left at room temperature for 3 h, and then placed at 4°C for 3, 9, or 21 h. There was a rapid marked fall in Ki67 staining of β-cells compared with those fixed immediately. Values at death were 6.9 ± 0.9% (n = 6) after a 24-h fast, 4.1 ± 0.9% (n = 6) at 3 h room temperature, 2.7 ± 0.7% (n = 5) at 6 h, 1.6 ± 0.6% (n = 5) at 12 h, and 2.9 ± 0.8% (n = 5) at 24 h. Similar postmortem conditions in newborn pigs resulted in very similar declines in Ki67 staining of their β-cells. These data support the hypothesis that conclusions on the lack of replication of adult human β-cells are incorrect and suggest that adult human β-cells replicate at a low but quantitatively meaningful rate.
format Online
Article
Text
id pubmed-4407864
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-44078642016-05-01 Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells Sullivan, Brooke A. Hollister-Lock, Jennifer Bonner-Weir, Susan Weir, Gordon C. Diabetes Islet Studies Some report that adult human β-cells do not replicate, but we postulate this assumption is erroneous due a postmortem decline in replication markers such as Ki67. Our earlier report showed that Ki67-marked β-cells were rarely found in human cadaveric pancreases but were in the range of 0.2–0.5% in human islets transplanted into mice. This study subjected 4-week-old mice to autopsy conditions that typically occur with humans. Mice were killed, left at room temperature for 3 h, and then placed at 4°C for 3, 9, or 21 h. There was a rapid marked fall in Ki67 staining of β-cells compared with those fixed immediately. Values at death were 6.9 ± 0.9% (n = 6) after a 24-h fast, 4.1 ± 0.9% (n = 6) at 3 h room temperature, 2.7 ± 0.7% (n = 5) at 6 h, 1.6 ± 0.6% (n = 5) at 12 h, and 2.9 ± 0.8% (n = 5) at 24 h. Similar postmortem conditions in newborn pigs resulted in very similar declines in Ki67 staining of their β-cells. These data support the hypothesis that conclusions on the lack of replication of adult human β-cells are incorrect and suggest that adult human β-cells replicate at a low but quantitatively meaningful rate. American Diabetes Association 2015-05 2014-12-08 /pmc/articles/PMC4407864/ /pubmed/25488899 http://dx.doi.org/10.2337/db14-1675 Text en © 2015 by the American Diabetes Association. Readers 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.
spellingShingle Islet Studies
Sullivan, Brooke A.
Hollister-Lock, Jennifer
Bonner-Weir, Susan
Weir, Gordon C.
Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title_full Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title_fullStr Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title_full_unstemmed Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title_short Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells
title_sort reduced ki67 staining in the postmortem state calls into question past conclusions about the lack of turnover of adult human β-cells
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407864/
https://www.ncbi.nlm.nih.gov/pubmed/25488899
http://dx.doi.org/10.2337/db14-1675
work_keys_str_mv AT sullivanbrookea reducedki67staininginthepostmortemstatecallsintoquestionpastconclusionsaboutthelackofturnoverofadulthumanbcells
AT hollisterlockjennifer reducedki67staininginthepostmortemstatecallsintoquestionpastconclusionsaboutthelackofturnoverofadulthumanbcells
AT bonnerweirsusan reducedki67staininginthepostmortemstatecallsintoquestionpastconclusionsaboutthelackofturnoverofadulthumanbcells
AT weirgordonc reducedki67staininginthepostmortemstatecallsintoquestionpastconclusionsaboutthelackofturnoverofadulthumanbcells