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

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 ther...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medical primatology 2015-08, Vol.44 (4), p.202-217
Main Authors: Frost, Patrice A., Chen, Shuyuan, Mezzles, Marguerite J., Voruganti, Venkata Saroja, Nava-Gonzalez, Edna J., Arriaga-Cazares, Hector E., Freed, Katy A., Comuzzie, Anthony G., DeFronzo, Ralph A., Kent Jr, Jack W., Grayburn, Paul A., Bastarrachea, Raul A.
Format: Article
Language:English
Subjects:
Administration, Intravenous
Animals
Blood Glucose - analysis
Catheters, Indwelling
Diabetes Mellitus, Experimental - etiology
Disease Models, Animal
fulminant type 1 diabetes
hydration protocol
hyperglucagonemia
Hyperglycemia
Hyperglycemia - chemically induced
hypoglycemia
hypoleptinemia
Insulin
Male
Papio hamadryas - metabolism
Streptozocin - administration & dosage
Streptozocin - pharmacology
triphasic blood glucose response
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0047-2565
1600-0684
DOI:10.1111/jmp.12182