Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2010 Oct;95(10):E234-9. doi: 10.1210/jc.2010-0932. Epub 2010 Jul 21.

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.

Author information

1
Diabetes Branch, National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK), National Institutes of Health, Bethesda, Maryland 20892, USA. perls@nhlbi.nih.gov

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00006505.

PMID:
20660050
PMCID:
PMC3050099
DOI:
10.1210/jc.2010-0932
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center