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

Yoshifumi Saisho, Erica Manesso, Alexandra E. Butler, Ryan Galasso, Kylie Kavanagh, Mickey Flynn, Li Zhang, Paige Clark, Tatyana Gurlo, Gianna M. Toffolo, Claudio Cobelli, Janice D. Wagner, Peter C. Butler

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)848-856
Number of pages9
JournalDiabetes
Volume60
Issue number3
DOIs
Publication statusPublished - 2011 Mar

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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