Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model

Patrice A. Frost, Shuyuan Chen, Marguerite J. Mezzles, Venkata Saroja Voruganti, Edna J. Nava-Gonzalez, Hector E. Arriaga-Cazares, Katy A. Freed, Anthony G. Comuzzie, Ralph A. Defronzo, Jack W. Kent, Paul A. Grayburn, Raul A. Bastarrachea

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Non-human primate (NHP) diabetic models using chemical ablation of β-cells with STZ have been achieved by several research groups. Chemotherapeutic STZ could lead to serious adverse events including nephrotoxicity, hepatotoxicity, and mortality. Methods: We implemented a comprehensive therapeutic strategy that included the tether system, permanent indwelling catheter implants, an aggressive hydration protocol, management for pain with IV nubain and anxiety with IV midazolam, moment-by-moment monitoring of glucose levels post-STZ administration, and continuous intravenous insulin therapy. Results: A triphasic response in blood glucose after STZ administration was fully characterized. A dangerous hypoglycemic phase was also detected in all baboons. Other significant findings were hyperglycemia associated with low levels of plasma leptin, insulin and C-peptide concentrations, hyperglucagonemia, and elevated non-esterified fatty acids (NEFA) concentrations. Conclusions: We successfully induced frank diabetes by IV administering a single dose of pharmaceutical-grade STZ safely and without adverse events in conscious tethered baboons.

Original languageEnglish (US)
Pages (from-to)202-217
Number of pages16
JournalJournal of medical primatology
Volume44
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Fulminant type 1 diabetes
  • Hydration protocol
  • Hyperglucagonemia
  • Hypoglycemia
  • Hypoleptinemia
  • Triphasic blood glucose response

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Fingerprint Dive into the research topics of 'Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model'. Together they form a unique fingerprint.

Cite this