Effect of different stimulators and a blocker of insulin release on islet Na+, K+-ATPase activity.

: The effect of several insulin secretagogues and a blocker upon islet Na+, K+-ATPase activity was studied using rat islet homogenates. None of the agents tested modified the enzyme activity when added directly to the enzyme assay. Activity of Na+, K+-ATPase measured in islets preincubated during 3 min with glucose 3.3, 8 or 16.6 mM, as well as with 15 mM KIC or 1.2 microM somatostatin, did not significantly change. The presence of glucagon (1.4 microM) plus theophylline (10 mM) in the preincubation medium significantly enhanced activity while tolbutamide (1.48 mM) or gliclazide (76 microM) significantly decreased such activity. These results suggest that Na+, K+-ATPase activity would not be a main common step involved in the mechanism by which glucose, KIC, glucagon + theophylline and somatostatin exert their effect on insulin secretion. Conversely, the enzyme might contribute to the stimulatory effect of gliclazide and tolbutamide on insulin release. Such effect would be secondary to the release of some cellular mediator rather than a direct action of these compounds on the enzyme. Such effect would later favor a rise in the cytosolic concentration of calcium which might trigger the release of insulin.