Significant Human β-Cell Turnover Is Limited to the First Three Decades of Life as Determined by in Vivo Thymidine Analog Incorporation and Radiocarbon Dating

Aims: Diabetes mellitus results from an absolute or relative deficiency of insulin-producing pancreatic beta-cells. The turnover rate of adult human beta-cells remains unknown. We employed two techniques to examine adult human islet beta-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 beta-cell turnover by scoring nuclear analog labeling within insulin-staining cells. Human adult beta-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 beta-cell DNA was obtained from two donors (ages 48 and 80 yr). 14C 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 beta-cell nuclei costained for BrdU/IdU. No beta-cell nuclei costained in the eight patients more than 30 yr old. Consistent with the BrdU/IdU turnover data, beta-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 beta-cells and their cellular precursors are established by young adulthood. (J Clin Endocrinol Metab 95: E234-E239, 2010)