Twenty-seven male New Zealand White rabbits were injected with a single dose of 10,000 IU E. coli L-asparaginase per kilogram body wt to document the diabetogenic activity of this antitumor agent. Significant weight loss was observed by day 1, and á loss continued until day 9. After day 16, weight steadily increased.
Random serum glucose levels increased steadily after the injection of L-asparaginase, reaching a peak value of 344 ± 32 mg/di ( ± SEM) on day 10. From day 12, levels declined, but they remained significantly higher than basal levels. Serum immunoreactive insulin (IRI) levels had a similar pattern of response. By day 2 the IRI was significantly above baseline. The IRI levels increased daily, reaching a peak level of 1379 ± 587 pg/ml ( ± SEM). Thereafter the levels fell gradually. However, the IRI levels remained significantly.higher than basal levels. Intravenous regular insulin decreased glucose levels in L-asparaginase–treated animals at 3 h by only 7.7 ± 3.2%, while it decreased them in controls by 34.0 ± 6.7% (P < 0.0025).
These data demonstrate that, acutely, a single intravenous dose of 10,000 IU E. coli L-asparaginase per kilogram body wt induces a hyperinsulinemic, insulin-resistant, diabetic syndrome in rabbits.