L-Asparaginase-induced diabetes mellitus in rabbits.
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 a 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/dl (x- +/- 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 1,379 +/- 587 pg/ml (x- +/- 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 less than 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.
D000818:Animals; D001215:Asparaginase / Q000494:pharmacology / Q000633:toxicity; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D008297:Male; D011817:Rabbits
D001786:Blood Glucose; D007328:Insulin; D001215:Asparaginase