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Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication

The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accum...

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Autores principales: Salpeter, Seth J., Khalaileh, Abed, Weinberg-Corem, Noa, Ziv, Oren, Glaser, Benjamin, Dor, Yuval
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717843/
https://www.ncbi.nlm.nih.gov/pubmed/23630298
http://dx.doi.org/10.2337/db13-0160
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author Salpeter, Seth J.
Khalaileh, Abed
Weinberg-Corem, Noa
Ziv, Oren
Glaser, Benjamin
Dor, Yuval
author_facet Salpeter, Seth J.
Khalaileh, Abed
Weinberg-Corem, Noa
Ziv, Oren
Glaser, Benjamin
Dor, Yuval
author_sort Salpeter, Seth J.
collection PubMed
description The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells. Old mice parabiosed to young mice have increased β-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old β-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients; conversely, young β-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/INK4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic β-cells.
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spelling pubmed-37178432014-08-01 Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication Salpeter, Seth J. Khalaileh, Abed Weinberg-Corem, Noa Ziv, Oren Glaser, Benjamin Dor, Yuval Diabetes Original Research The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells. Old mice parabiosed to young mice have increased β-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old β-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients; conversely, young β-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/INK4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic β-cells. American Diabetes Association 2013-08 2013-07-17 /pmc/articles/PMC3717843/ /pubmed/23630298 http://dx.doi.org/10.2337/db13-0160 Text en © 2013 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Salpeter, Seth J.
Khalaileh, Abed
Weinberg-Corem, Noa
Ziv, Oren
Glaser, Benjamin
Dor, Yuval
Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title_full Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title_fullStr Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title_full_unstemmed Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title_short Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
title_sort systemic regulation of the age-related decline of pancreatic β-cell replication
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717843/
https://www.ncbi.nlm.nih.gov/pubmed/23630298
http://dx.doi.org/10.2337/db13-0160
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