| Summary: | 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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