Accelerated telomere shortening and senescence in human pancreatic islet cells stimulated to divide in vitro

in Journal of Endocrinology
Authors:
TL Halvorsen
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GM Beattie
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AD Lopez
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A Hayek
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F Levine
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DOI:
https://doi.org/10.1677/joe.0.1660103
Volume/Issue:
Volume 166: Issue 1
Article Type:
Other
Page Range:
103–109
Online Publication Date:
01 Jul 2000
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Widespread application of beta-cell replacement strategies for diabetes is dependent upon the availability of an unlimited supply of cells exhibiting appropriate glucose-responsive insulin secretion. Therefore, a great deal of effort has been focused on understanding the factors that control beta-cell growth. Previously, we found that human beta-cell-enriched islet cultures can be stimulated to proliferate, but expansion was limited by growth arrest after 10-15 cell divisions. Here, we have investigated the mechanism behind the growth arrest. Our studies, including analyses of the expression of senescence-associated beta-galactosidase, p16(INK4a) levels, and telomere lengths, indicate that cellular senescence is responsible for limiting the number of cell divisions that human beta-cells can undergo. The senescent phenotype was not prevented by retroviral transduction of the hTERT gene, although telomerase activity was induced. These results have implications for the use of primary human islet cells in cell transplantation therapies for diabetes.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
7
Article Type:
Other
Print Publication Date:
01 Jul 2000
Online Publication Date:
01 Jul 2000