Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes

Y Saisho, E Manesso, AE Butler, R Galasso… - Diabetes, 2011 - Am Diabetes Assoc
Y Saisho, E Manesso, AE Butler, R Galasso, K Kavanagh, M Flynn, L Zhang, P Clark…
Diabetes, 2011Am Diabetes Assoc
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 …
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.
Am Diabetes Assoc