Document Detail


Glucose and aging control the quiescence period that follows pancreatic beta cell replication.
MedLine Citation:
PMID:  20823063     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pancreatic beta cell proliferation has emerged as the principal mechanism for homeostatic maintenance of beta cell mass during adult life. This underscores the importance of understanding the mechanisms of beta cell replication and suggests novel approaches for regenerative therapy to treat diabetes. Here we use an in vivo pulse-chase labeling assay to investigate the replication dynamics of adult mouse beta cells. We find that replicated beta cells are able to re-enter the cell division cycle shortly after mitosis and regain their normal proliferative potential after a short quiescence period of several days. This quiescence period is lengthened with advanced age, but shortened during injury-driven beta cell regeneration and following treatment with a pharmacological activator of glucokinase, providing strong evidence that metabolic demand is a key determinant of cell cycle re-entry. Lastly, we show that cyclin D2, a crucial factor in beta cell replication, is downregulated during cell division, and is slowly upregulated post-mitosis by a glucose-sensitive mechanism. These results demonstrate that beta cells quickly regain their capacity to re-enter the cell cycle post-mitosis and implicate glucose control of cyclin D2 expression in the regulation of this process.
Authors:
Seth J Salpeter; Allon M Klein; Danwei Huangfu; Joseph Grimsby; Yuval Dor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  137     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2010-10-12     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  3205-13     Citation Subset:  IM    
Affiliation:
Department of Developmental Biology and Cancer Research and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Aging
Animals
Cell Aging*
Cell Cycle
Cell Proliferation
Cyclin D2 / metabolism
Glucose / metabolism*
Insulin-Secreting Cells / cytology,  metabolism*
Mice
Chemical
Reg. No./Substance:
0/Cyclin D2; 50-99-7/Glucose
Comments/Corrections

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