EFFECT OF GLUCOSE-SULFONYLUREA INTERACTION ON RELEASE OF INSULIN, GLUCAGON, AND SOMATOSTATIN FROM ISOLATED PERFUSED RAT PANCREAS

The effect of a sulfonylurea, glibenclamide, on the release of insulin, glucagon, and somatostatin was studied in the isolated perfused rat pancreas. At glucose concentrations of 1.1 mM or less, the drug stimulated somatostatin release, whereas glucagon release, after 2-3 min of increase, was markedly inhibited. Insulin release was moderately stimulated, and maximal release occurred relatively late. A moderate glucose load (6.7 mM) inhibited glibenclamide-induced release of somatostatin, whereas the two in combination exerted an additive action on insulin release. Greater glucose loads, which by themselves would stimulate somatostatin release, only marginally suppressed glibenclamide-induced somatostatin release. The insulinogenic effect of these glucose levels was not modified by glibenclamide. Glibenclamide may thus stimulate both the alpha and beta as well as delta cells of the pancreas, depending on glucose concentration. We suggest a paracrine (local) interaction of somatostatin with the alpha and beta cells, which has an important role in the kinetics of insulin and glucagon release induced by sulfonylureas.