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

OBJECTIVE: \u3b2-Cell turnover and its potential to permit \u3b2-cell regeneration in adult primates are unknown. Our aims were 1) to measure \u3b2-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of \u3b2-cell replication and formation of new \u3b2-cells from other precursors (defined thus as \u3b2-cell neogenesis); and 3) to establish whether there is an adaptive increase in \u3b2-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. \u3b2-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS: \u3b2-Cell turnover is present in adult nonhuman primates (3.3 \ub1 0.9 mg/month), mostly (~80%) derived from \u3b2-cell neogenesis. \u3b2-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, \u3b2-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS: There is ongoing \u3b2-cell turnover in adult nonhuman primates that cannot be accounted for by \u3b2-cell replication. There is no evidence of \u3b2-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce \u3b2-cell apoptosis in nonhuman primates in vivo