- Saisho, Yoshifumi;
- Manesso, Erica;
- Butler, Alexandra E;
- Galasso, Ryan;
- Kavanagh, Kylie;
- Flynn, Mickey;
- Zhang, Li;
- Clark, Paige;
- Gurlo, Tatyana;
- Toffolo, Gianna M;
- Cobelli, Claudio;
- Wagner, Janice D;
- Butler, Peter C
Objective
β-Cell turnover and its potential to permit β-cell regeneration in adult primates are unknown. Our aims were 1) to measure β-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of β-cell replication and formation of new β-cells from other precursors (defined thus as β-cell neogenesis); and 3) to establish whether there is an adaptive increase in β-cell formation (attempted regeneration) in streptozotocin (STZ)-induced diabetes in adult nonhuman primates.Research design and methods
Adult (aged 7 years) vervet monkeys were administered STZ (45-55 mg/kg, n = 7) or saline (n = 9). Pancreas was obtained from each animal twice, first by open surgical biopsy and then by euthanasia. β-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates.Results
β-Cell turnover is present in adult nonhuman primates (3.3 ± 0.9 mg/month), mostly (~80%) derived from β-cell neogenesis. β-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, β-cell apoptosis was not increased in monkeys administered STZ.Conclusions
There is ongoing β-cell turnover in adult nonhuman primates that cannot be accounted for by β-cell replication. There is no evidence of β-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce β-cell apoptosis in nonhuman primates in vivo.