Significant Human β-Cell Turnover Is Limited to the First Three Decades of Life as Determined byin VivoThymidine Analog Incorporation and Radiocarbon Dating

• DOI: 10.1210/jc.2010-0932
• Publication Date: 2010-07-22T01:33:57Z
• 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
• Keywords: Adult; Male; Aging; Adolescent; Staining and Labeling; Radiometric Dating; Middle Aged; Tissue Donors; 3. Good health; Young Adult; Bromodeoxyuridine; Insulin-Secreting Cells; Humans; Female; Aged; Cell Proliferation; Thymidine

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.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.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.Under typical circumstances, human β-cells and their cellular precursors are established by young adulthood.