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.

Key words

Isolated Perfused Pancreas - Tolbutamide Effect - Insulin Secretion - Glucagon Depression - Streptozotocin Action

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)

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)

2 Fellow of Alexander von Humboldt Stiftung.

3 Assoc. Prof, of Medicine, University of Colorado Medical Center, and Visiting Prof, in 1970 at the University of Ulm.

4 Supported by Deutsche Forschungsgemeinschaft, Bad Godesberg (Pf 38/24).