Interaction of cyclic AMP and alloxan on insulin secretion in isolated rat islets perifused in vitro

The interaction of alloxan and cyclic AMP on glucose-induced insulin secretion was studied with the use of isolated rat islet perifusion. Simultaneous perifusion with cyclic AMP and alloxan did not protect the islets against the effect of alloxan. However, addition of dibutyryl cyclic AMP to the alloxan solution produced 40% protection of glucose-induced insulin secretion. Partial protection was obtained with either theophylline (41%) or caffeine alone (54%), and the addition of 1 mg/ml glucose to the theophylline or caffeine solution provided greater than 68% protection. The levels of islet tissue cyclic AMP were more than 2.1 times that of islets not protected against the alloxan effect, when partial or nearly complete reversal of the inhibitory action of alloxan on glucose-induced insulin secretion was effected by theophylline or caffeine. These results suggest that cyclic AMP affords partial protection against the effect of alloxan on glucose-induced insulin secretion.