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- Title
Successful pharmaceutical-grade streptozotocin ( STZ)-induced hyperglycemia in a conscious tethered baboon ( Papio hamadryas) model.
- 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, Jack W.; Grayburn, Paul A.; Bastarrachea, Raul A.
- 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.
- Subjects
STREPTOZOTOCIN; PHARMACEUTICAL research; HYPERGLYCEMIA; HAMADRYAS baboon; BLOOD sugar
- Publication
Journal of Medical Primatology, 2015, Vol 44, Issue 4, p202
- ISSN
0047-2565
- Publication type
Article
- DOI
10.1111/jmp.12182