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

Frost, Patrice A. y Chen, Shuyuan y Mezzles, Marguerite J. y Voruganti, Venkata Saroja y Nava González, Edna Judith y Arriaga Cazares, Hector E. y Freed, Katy A. y Comuzzie, Anthony G. y DeFronzo, Ralph A. y Kent, Jack W. y Grayburn, Paul A. y Bastarrachea, Raúl A. (2015) Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model. Journal of Medical Primatology, 44 (4). pp. 202-217. ISSN 00472565

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Resumen

Background Non-human primate (NHP) diabetic models using chemical ablation of b-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.

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