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

Abstract

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. b-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 b-cell apoptosis in nonhuman primates in vivo. © 2011 by the American Diabetes Association.