Combined effects of a calcium-agonist and hypoglycemic or hyperglycemic sulfonamides upon insulin release

The organic calcium-agonist CGP 28392 augmented insulin release evoked by D-glucose in rat pancreatic islets incubated in the presence or absence of gliclazide, but failed to stimulate insulin secretion in the absence of glucose or presence of diazoxide. Gliclazide, however, failed to augment insulin release evoked, in the presence of CGP 28392, by a high concentration of glucose (11.1 mM), and protected the B-cell against the inhibitory action of diazoxide. As judged from the relative magnitude of changes in 45Ca fractional outflow rate from prelabelled islets perifused at an intermediate glucose concentration (7.0 mM), CGP 28392 failed to affect the rapid cationic response to gliclazide, whereas this hypoglycemic sulfonylurea decreased the cationic response to CGP 28392. These results suggest that the functional response to gliclazide is attributable to a molecular mechanism distinct from the prolongation of the open time of calcium channels presumably provoked by the dihydropyridine.