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 ¹⁴C. 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). ¹⁴C levels were then determined using accelerator mass spectrometry. Cellular “birth date” was determined by comparing the subject’s DNA ¹⁴C content relative to a well-established ¹⁴C 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 ¹⁴C 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.