E. coli L-asparaginase and insulin release in vitro

Glucose induced insulin release, from collagenase isolated islets of Langerhans obtained from non diabetic male New Zealand White rabbits, was inhibited in vitro by E. coli L-asparatinase. This inhibition was time and dose dependent with maximal inhibition being attained after 1 1/2 hr incubation using a dose of 1000 I.U. L-asparaginase/ml. Tolbutamide potentiated glucose-induced insulin release in the presence of inhibitory doses of the L-asparaginase. This potentiation was decreased at higher dose levels of L-asparaginase. L-leucine, L-arginine and theophylline also potentiated glucose-induced insulin release in the presence of L-asparaginase. This potentiation was intact in the presence of all doses of L-asparaginase tested. Glucose induced insulin release, from collagense isolated islets obtained from male New Zealand White rabbits rendered hypoinsulinemic and diabetic by daily intravenous injections of L-asparaginase in vivo, was similar to that of islets of non diabetic control rabbits when the islets were incubated in vitro in te absence of L-asparaginase. These data suggest that the hypoinsulinemic diabetic syndrome produced by the anti-tumor enzyme, L-asparaginase, is produced at least in part by the suppression of insulin release and that this suppression requires the enzyme to be present.