Document Detail

Cell cycle control of β-cell replication in the prenatal and postnatal human pancreas.
MedLine Citation:
PMID:  20978233     Owner:  NLM     Status:  MEDLINE    
β-Cell regeneration declines with aging, but the molecular mechanisms controlling β-cell replication in humans are not well understood. We compared the expression of selected cell cycle proteins in prenatal and adult tissue and examined the association of these proteins with β-cell replication. Pancreatic tissue from a total of 20 human fetuses and adults was stained for Ki67, cyclin D3, p16 and p27, and insulin. The β-cellular expression of these cell cycle proteins was determined. The frequency of β-cell replication was lower in adult compared with prenatal β-cells (<0.5 vs. 3.4 ± 0.5%, respectively; P < 0.0001). p16 was sporadically expressed in prenatal β-cells (8.0 ± 1.1%) but highly enriched in adult β-cells (63.1 ± 5.2%, P < 0.0001). Likewise, the expression of p27 was much lower in prenatal β-cells (1.7 ± 0.4 vs. 44.1 ± 5.4%, respectively, P < 0.0001), and cyclin D3 expression increased from 24.2 ± 4.1 to 47.25 ± 5.0%, respectively (P < 0.001), with aging. The expression of all three proteins was significantly correlated with each other (P < 0.01 and r > 0.75, respectively). The strong expression of cyclin D3 in adult human β-cells and its correlation to p27 and p16 suggest a positive role in human β-cell cycle regulation. p16 and p27 appear to restrict β-cell replication with aging. The age dependency of cell cycle regulation in human β-cells might explain the reduced β-cell regeneration in adult humans.
Christina U Köhler; Marvin Olewinski; Andrea Tannapfel; Wolfgang E Schmidt; Helga Fritsch; Juris J Meier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-26
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  300     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-29     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E221-30     Citation Subset:  IM    
Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, Gudrunstr. 56, 44791 Bochum, Germany.
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MeSH Terms
Aged, 80 and over
Cell Cycle*
Cell Cycle Proteins / metabolism*
Cell Division
Cyclin D3 / metabolism
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Gestational Age
Insulin / metabolism
Insulin-Secreting Cells / cytology*,  metabolism*
Ki-67 Antigen / metabolism
Middle Aged
Pancreas / cytology,  embryology*,  growth & development*,  metabolism
Reg. No./Substance:
0/CCND3 protein, human; 0/Cell Cycle Proteins; 0/Cyclin D3; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Ki-67 Antigen; 11061-68-0/Insulin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27

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