Summary
The diabetogenic effect of daily injections of 1000 i.u./kg body wt. E coli L-asparaginase was studied in male New Zealand white rabbits and compared with the
diabetogenic effect of a single bolus of 10,000 I.U. E coli L-asparaginase/kg body wt. to determine whether the schedule of administration of
the drug altered the diabetic syndrome produced. A daily injection of 1000 i.u. L-asparaginase/kg.
body wt. was continued for 30 days. During this time glucose levels in rabbits allowed
free access to food rose steadily, reaching levels of 717±63 mg/dl the day after the
last injection. Levels of immunoreactive insulin fell, reaching their nadir, 53±4
pg/ml (approximately 50% of baseline) at 25 days. Glucose levels declined when therapy
was discontinued, but remained significantly above control levels 46 days after insulin
injections were stopped. (Glucose levels in L-asparaginase-treated groups vs. those
in controls on day 46 after discontinuation: 116±3 vs. 104± 1 mg/dl; P < 0.0025.)
Levels of immunoreactive insulin rose when therapy ended, reaching control levels
17 days after discontinuation. In contrast, a single bolus injection of 10,000 I.U.
L-asparaginase/kg resulted in hyperglycemia with hyperinsulinemia. These data suggest
that L-asparaginase can induce either a hypoinsulinemic or a hyperinsulinemic diabetic
syndrome depending on the schedule of administration of the L-asparaginase and that
a mild abnormality in glucose homeostasis persists after discontinuation of L-asparaginase
therapy.
Key-Words:
Diabetes Mellitus
-
Rabbits
-
Hyperinsulinemic
-
Hypoinsulinemic
-
L-Asparaginase
