Document Detail


Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating.
MedLine Citation:
PMID:  20660050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Diabetes mellitus results from an absolute or relative deficiency of insulin-producing pancreatic β-cells. The turnover rate of adult human β-cells remains unknown. We employed two techniques to examine adult human islet β-cell turnover and longevity in vivo.
METHODS: Subjects enrolled in National Institutes of Health clinical trials received thymidine analogs [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8 d to 4 yr prior to death. Archival autopsy samples from 10 patients (aged 17-74 yr) were employed to assess β-cell turnover by scoring nuclear analog labeling within insulin-staining cells. Human adult β-cell longevity was determined by estimating the cells' genomic DNA integration of atmospheric (14)C. DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15-yr-old donor, and purified β-cell DNA was obtained from two donors (ages 48 and 80 yr). (14)C levels were then determined using accelerator mass spectrometry. Cellular "birth date" was determined by comparing the subject's DNA (14)C content relative to a well-established (14)C atmospheric prevalence curve.
RESULTS: In the two subjects less than 20 yr of age, 1-2% of the β-cell nuclei costained for BrdU/IdU. No β-cell nuclei costained in the eight patients more than 30 yr old. Consistent with the BrdU/IdU turnover data, β-cell DNA (14)C content indicated that the "birth date" of cells occurred within the subject's first 30 yr of life.
CONCLUSIONS: Under typical circumstances, human β-cells and their cellular precursors are established by young adulthood.
Authors:
S Perl; J A Kushner; B A Buchholz; A K Meeker; G M Stein; M Hsieh; M Kirby; S Pechhold; E H Liu; D M Harlan; J F Tisdale
Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-07-21
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-07     Completed Date:  2010-11-15     Revised Date:  2013-03-28    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E234-9     Citation Subset:  AIM; IM    
Affiliation:
Diabetes Branch, National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK), National Institutes of Health, Bethesda, Maryland 20892, USA. perls@nhlbi.nih.gov
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00006505
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aging / metabolism,  physiology*
Bromodeoxyuridine / pharmacokinetics*
Cell Proliferation*
Female
Humans
Insulin-Secreting Cells / metabolism,  physiology*
Male
Middle Aged
Radiometric Dating* / methods
Staining and Labeling / methods
Thymidine / analogs & derivatives,  pharmacokinetics
Tissue Donors
Young Adult
Grant Support
ID/Acronym/Agency:
RR13461/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
50-89-5/Thymidine; 59-14-3/Bromodeoxyuridine
Comments/Corrections
Comment In:
J Clin Endocrinol Metab. 2010 Oct;95(10):4552-4   [PMID:  20926542 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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