title: Ongoing beta-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.
  
  
  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.
authors.affiliation: Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saisho
authors.forename: Erica
authors.initials: E
authors.lastname: Manesso
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Butler
authors.forename: Ryan
authors.initials: R
authors.lastname: Galasso
authors.forename: Kylie
authors.initials: K
authors.lastname: Kavanagh
authors.forename: Mickey
authors.initials: M
authors.lastname: Flynn
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Paige
authors.initials: P
authors.lastname: Clark
authors.forename: Tatyana
authors.initials: T
authors.lastname: Gurlo
authors.forename: Gianna M
authors.initials: GM
authors.lastname: Toffolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Janice D
authors.initials: JD
authors.lastname: Wagner
authors.forename: Peter C
authors.initials: PC
authors.lastname: Butler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002096:C-Peptide / Q000097:blood; D002455:Cell Division / Q000502:physiology; D002522:Chlorocebus aethiops; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D013311:Streptozocin
chemical_list: D002096:C-Peptide; D007328:Insulin; D013311:Streptozocin