Effects of Tolbutamide on Insulin and Glucagon Secretion of the Isolated Perfused Rat Pancreas

Abstract

Insulin and glucagon release in the isolated perfused rat pancreas was measured after stimulation with tolbutamide. The perfusion medium contained either 5.5 mM of glucose or was glucose free. During the first ten min of perfusion with tolbutamide, insulin output rose rapidly while glucagon release was significantly depressed. After a period of prolonged stimulation glucagon began rising again but did not return to initial levels. Following destruction of insulin-producing Bcells by streptozotocin, tolbutamide still caused identical inhibition of glucagon secretion, as in the presence of intact islets. A significant inverse relationship between insulin and glucagon output seemed to be established. Yet, despite the fact that considerably higher insulin levels were kept in the presence of 5.5 mM glucose in the perfusate, tolbutamide effected about the same depression of glucagon quantitatively as in the presence of low insulin levels. Tolbutamide seems to block the glucagon releasing mechanism independent of the functional state of B-cells. 1 Presented in part at the 6th Congress of the European Association for the Study of Diabetes, Warsaw, 1970, and published in abstract form in Diabetologia 6: 636 (1970)