title: Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin: adverse effects and early responses.
abstract: OBJECTIVE
  Streptozotocin (STZ) has been widely used to induce diabetes in nonhuman primates, although it has been found difficult to achieve complete diabetes without serious adverse effects. We have investigated different types and dosages of STZ to find a way to safely induce complete diabetes in cynomolgus monkeys.
  
  
  METHODS
  After adequate hydration, 10 monkeys received STZ. Five monkeys received conventional STZ (Sigma) at a dosage of 1250 mg/m ("high dose"; n = 4) or 60 mg/kg ("low dose"; n = 1; Group 1). Five monkeys received Zanosar STZ (Sicor Pharmaceuticals, Irvine, CA) at 150 mg/kg (high dose; n = 5; Group 2).
  
  
  RESULTS
  High-dose Group 1 monkeys became completely diabetic (n = 4), but a protein-losing nephropathy was observed in 3 of the 4 monkeys. The monkey that received 60 mg/kg STZ failed to become fully diabetic (C-peptide, > 1.86 ng/mL). Group 2 (high-dose Zanosar-treated) monkeys became completely diabetic but with no apparent adverse effects. A triphasic blood glucose response to STZ was documented in all the high-dose STZ-treated monkeys. Low-dose STZ failed to result in a triphasic response.
  
  
  CONCLUSIONS
  (1) High-dose Zanosar STZ induced diabetes safely in cynomolgus monkeys without adverse effects. (2) A triphasic blood glucose response suggested the complete induction of diabetes.
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Pleunie P M
authors.initials: PP
authors.lastname: Rood
authors.forename: Rita
authors.initials: R
authors.lastname: Bottino
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.forename: Cindy
authors.initials: C
authors.lastname: Smetanka
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Jamie
authors.initials: J
authors.lastname: Busch
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D012016:Reference Values; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D002096:C-Peptide; D013311:Streptozocin