Effect of salicylate poisoning on insulin secretion. Studies on its mechanism of action.

Sodium salicylate poisoning increased glucose-induced insulin secretion by slices of rat pancreas. The alpha adrenergic blocker phentolamine, but not salicylate poisoning, overcame the inhibitory effect of epinephrine on insulin secretion. Theophylline (5, 10 and 15 mM) significantly increased the insulin secretion induced by 11 mM glucose. The highest insulin response was obtained when theophylline was used at a 10 mM concentration. However, when pancreas slices from salicylate poisoned rats were used, a 5 mM concentration was sufficient to achieve maximal insulin response. Salicylate poisoning diminished the free tubulin pool, an action that was impaired by imidazole; however, imidazole did not modify the effect of the ionophore A23187. The results suggest that: a) sodium salicylate poisoning increases B-cell response to glucose; b) changes in alpha adrenergic activity are not related to the mechanism of action of salicylate; c) an increment in the cAMP concentration may mediate the stimulatory effect of salicylate poisoning on insulin secretion; d) the effect of salicylate on the microtubular system is indirect and probably mediated through an increment in pancreatic cAMP.