GLICLAZIDE DIRECTLY SUPPRESSES ARGININE-INDUCED GLUCAGON-SECRETION

To clarify whether the effect of sulfonylurea on glucagon secretion is directly on the pancreatic A cell, we examined changes produced by gl iclazide in glucagon (IRG), insulin (IRI) and somatostatin (IRS) relea se from the isolated perfused rat pancreas. Under 5 mM glucose infusio n, IRI and IRS were increased by gliclazide in a dose-dependent manner , but IRG was unchanged. When 20 mM arginine was infused to stimulate glucagon secretion, both IRI and IRG increased markedly in a biphasic fashion and IRS increased slightly. The administration of gliclazide a t the time of second phase response of IRG, IRI and IRS increased furt her and IRG decreased at every dose used. Insulin administration to th e control and streptozotocin-treated rat pancreas did not change argin ine-induced IRG secretion. Gliclazide-induced glucagon suppression was also observed in streptozotocin-diabetic rat pancreas. The amount of administered somatostatin required for inhibiting glucagon secretion w as higher than the maximal level obtained from endogenous secretion of somatostatin after gliclazide. Neither cysteamine treatment alone (so matostatin-depleted) nor combined with streptozotocin-treatment (combi ned;depletion of somatostatin and insulin) changed gliclazide-induced glucagon suppression. Thus, it is concluded that suppression of glucag on is induced by sulfonylurea itself