Effects of Anti-Microtubular Agents on Alloxan Stimulation and Inhibition of Glucose-Induced Insulin Release in Vitro

The effect of various anti-microtubular agents on alloxan stimulation and inhibition of a subsequent glucose-induced insulin release was investigated using in vitro incubation and perifusion of rat isolated islets of Langerhans. Five minute exposure of islets to alloxan (20 mg/dl) induced a transient burst of insulin release which was eliminated by the pretreatment of islets by heavy water (D2O) or colchicine (10-3 M) and concomitant presence of them with alloxan. However, vincristine (10-4 M) did not affect alloxan actions.

A brief exposure .of islets to alloxan completely inhibited a subsequent glucose (16.7 mM)-induced insulin release. The pretreatment of islets with D2O or colchicine prevented alloxan inhibition of insulin release, whereas vincristine did not demonstrate
such an action.

Because the transport of pyrimidine was completely inhibited by anti-microtubular agents, it seems likely that the transport of alloxan (2, 4, 5, 6-tetraoxypyrimidine, 5, 6-dioxyuracil) into the B-cell is impaired by these agents. Otherwise, anti-microtubular agents reduced the generation of highly reactive oxygen-containing free radicals from alloxan, which inhibits the glucose-induced insulin release.