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Successful pharmaceutical‐grade streptozotocin ( STZ )‐induced hyperglycemia in a conscious tethered baboon ( P apio hamadryas ) model
Author(s) -
Frost Patrice A.,
Chen Shuyuan,
Mezzles Marguerite J.,
Voruganti Venkata Saroja,
NavaGonzalez Edna J.,
ArriagaCazares Hector E.,
Freed Katy A.,
Comuzzie Anthony G.,
DeFronzo Ralph A.,
Kent Jack W.,
Grayburn Paul A.,
Bastarrachea Raul A.
Publication year - 2015
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/jmp.12182
Subject(s) - streptozotocin , medicine , adverse effect , diabetes mellitus , insulin , nefa , endocrinology , leptin , baboon , pharmacology , obesity
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.