Ongoing β-Cell Turnover in Adult Nonhuman Primates Is Not Adaptively Increased in Streptozotocin-Induced Diabetes

OBJECTIVE-beta-Cell turnover and its potential to permit beta-cell regeneration in adult primates are unknown. Our aims were 1) to measure beta-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of beta-cell replication and formation of new beta-cells from other precursors (defined thus as beta-cell neogenesis); and 3) to establish whether there is an adaptive increase in beta-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. beta-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS-beta-Cell turnover is present in adult nonhuman primates (3.3 +/- 0.9 mg/month), mostly (similar to 80%) derived from beta-cell neogenesis. beta-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, beta-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS-There is ongoing beta-cell turnover in adult nonhuman primates that cannot be accounted for by beta-cell replication. There is no evidence of beta-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce beta-cell apoptosis in nonhuman primates in vivo. Diabetes 60:848-856, 2011