title: Characterization and validation of a streptozotocin-induced diabetes model in the vervet monkey.
abstract: BACKGROUND
  Streptozotocin (STZ), preferentially toxic to pancreatic beta cells, is commonly used to model Type 1 diabetes mellitus (DM) in numerous species, including nonhuman primates.
  
  
  METHODS
  We induced DM in twenty vervet monkeys (Chlorocebus aethiops) by intravenous administration of either 45 (n=8, STZ-45) or 55 mg/kg STZ (n=12, STZ-55); ten control (CTL) monkeys received saline.
  
  
  RESULTS
  Overall there was 15% mortality, likely secondary to renal toxicity. Twice-daily insulin therapy was initiated to maintain comparable glycemic control, confirmed by comparable glycated hemoglobin levels. Exogenous insulin requirements increased rapidly for 4weeks; STZ-45 insulin doses stabilized thereafter while STZ-55 doses continued to increase through 16weeks. Glucose tolerance testing and arginine-stimulated insulin secretion confirmed 80-90% reduction in pancreatic beta cell function in both groups. Body weight was reduced in all STZ monkeys, with return to baseline only in STZ-45 at 16 wks. Elevated blood urea nitrogen (BUN) and creatinine were noted in the STZ-55 group. Alkaline phosphatase (ALKP) was also increased with STZ-55 (p < 0.05 vs. CTL) whereas STZ-45 ALKP elevation resolved by study end. Red cell parameters were reduced in all STZ monkeys, but more severely in the STZ-55 group.
  
  
  CONCLUSIONS
  We have demonstrated that a model of DM can be induced and maintained in vervets with a single dose of STZ. The lower dose of STZ (45 mg/kg) significantly improved the toxicity profile without altering efficacy in inducing DM. Finally, sufficient time following induction is recommended to allow transient renal, hepatic and hematologic parameters to resolve.
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. kkavanag@wfubmc.edu
authors.forename: Kylie
authors.initials: K
authors.lastname: Kavanagh
authors.forename: David M
authors.initials: DM
authors.lastname: Flynn
authors.forename: Chris
authors.initials: C
authors.lastname: Nelson
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Janice D
authors.initials: JD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002522:Chlorocebus aethiops; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D001120:Arginine