Effect of methylxanthines on alloxan inhibition of insulin release.

Isloated rat islets were maintained in vitro in a perifusion system, exposed to alloxan (20 mg/100 ml) for 5 minutes in the presence of agents which affect cAMP metabolism and subsequently stimulated with glucose. The rate of insulin secretion was monitored throughout the period of perifusion. Exposure to alloxan alone produces complete inhibition of glucose-induced insulin release [18] whereas concomitant exposure to carreine and theophylline for this brief interval provided almost complete protection of the islets from the inhibitory action of alloxan. Glucagon, cAMP and CBcAMP did not protect the islets form alloxan. Pre-treatment of the islets with either theophylline or glucagon and DBcAMP did not provide protection. These findings indicate that the protective action of theophylline and carreine against alloxan is unrelated to the effect of these agents on cAMP metabolism in the beta cell.