| Accelerated telomere shortening and senescence in human pancreatic islet cells stimulated to divide in vitro. | |
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MedLine Citation:
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PMID: 10856888 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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T L Halvorsen; G M Beattie; A D Lopez; A Hayek; F Levine |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of endocrinology Volume: 166 ISSN: 0022-0795 ISO Abbreviation: J. Endocrinol. Publication Date: 2000 Jul |
Date Detail:
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Created Date: 2000-08-17 Completed Date: 2000-08-17 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0375363 Medline TA: J Endocrinol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 103-9 Citation Subset: IM |
Affiliation:
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Center for Molecular Genetics, University of California San Diego School of Medicine, San Diego, California 92093-0634, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Carrier Proteins / analysis Cell Aging Cell Cycle Proteins* Cell Division Cells, Cultured Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p16* DNA-Binding Proteins Diabetes Mellitus, Type 1 / surgery Enzyme Induction Female Humans Islets of Langerhans / enzymology, ultrastructure* Male Middle Aged RNA* Telomerase / biosynthesis, genetics Telomere / ultrastructure* Transfection Tumor Suppressor Proteins* beta-Galactosidase / analysis |
| Grant Support | |
ID/Acronym/Agency:
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DK55065/DK/NIDDK NIH HHS; DK55283/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CDKN2B protein, human; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA-Binding Proteins; 0/Tumor Suppressor Proteins; 0/telomerase RNA; 63231-63-0/RNA; EC 2.7.7.49/Telomerase; EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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