90 EFFECT OF SODIUM SALICYLATE ON INSULIN SECRETION: STUDIES ON THE MECHANISM OF ACTION

The curve that depicts the inter-relation of different glucose concentrations(5.5 to 27.5mM) to the insulin response is shifted to the left by the addition of sodium salicylate(1.87mM) when incubation of pancreas slices are used. Phentolamine but not sodium salicylate, overcomes the inhibitory effect of epinephine on insulin secretion induced by glucose. The highest insulin response is obtained by theophylline or pentoxyfilline at 10mM concentrations (in the presence of glucose 11mM). When sodium salicylate is present in the incubation medium, only 5 mM theophylline or pentosyfine plus 11 mM glucose achives the highest insulin response. Salicylate lower the free tubulin pool an action that is impaired by imidazole; however imidazole does not impaire the effect of A23187. The results shown suggest: a) sodium salicylate increases beta cell sensitivity to glucose, b) adrenergic tone modifications are not related to the salicylate mechanism of action c) an increment in the cAMP production seems to be the main way by which salicilate increases insulin secretion, d) the effect of salicylate on the microtubular system are indirect and mediated through an increment of the pancreatic cAMP.