[Serum immunoreactive insulin after the oral administration of single dose of tolbutamide. II. Pancreatic vein immunoreactive insulin in dogs (author's transl)].

The mode of action of sulfonylureas as hypoglycemic agent is not clarified yet. But it has been said in general to act by increasing the secretion of insulin from the beta cells. While, some believe that their effect is independent on insulin secretion. In the previous report, it was demonstrated that the oral administration of single dose of tolbutamide failed to increase immunoreactive insulin (IRI) in the peripheral vein in spite of significant decrease of blood glucose and free fatty acid levels both in normal and diabetic subjects. In order to observe changes of IRI level in the pancreatic vein following the oral administration of single dose of tolbutamide, the present study was carried out to determine serum IRI level of the pancreatic and peripheral vein in dogs. Mongrel dogs of both sexes, weighing 7-12 kg were anesthetized with sodium pentobarbital. A catheter was inserted into the superior pancreatico-duodenal vein through its duodenal branch after a laparotomy. Another catheter was inserted into the femoral vein for the collection of peripheral venous blood. The experiment was started one hour after the operation. Blood glucose level decreased gradually to 39 per cent reduction of the previous level at 180 minutes after intragastric administration of single dose of tolbutamide (0.1 g per kg). Serum IRI level in the peripheral vein showed only slight increase, similar to the response in man. While, pancreatic vein IRI level increased gradually and showed a fourfold increment after 180 minutes (from 143 muU per ml to 556 muU per ml), associated with a constant elevation of plasma tolbutamide concentration which showed 6.4 mg per 100 ml after 180 minutes. Simultaneous administration of 0.1 g per kg of tolbutamide and the same dose of sodium bicarbonate caused 49 per cent reduction of blood glucose level and a doubling of the basal IRI level in the peripheral vein. Serum IRI level in the pancreatic vein rose sharply and demonstrated a peak at 90 minutes (620 per cent increase). The elevation of plasma tolbutamide concentration was somewhat more rapid than that after tolbutamide alone. From these observations, it was confirmed that an apparent secretion of insulin into the pancreatic vein was induced by the oral administration of tolbutamide alone, in spite of the lack of increase in the peripheral vein IRI. And it is emphasized that the changes of insulin level in the pancreatic vein should be taken into account in a study of insulin dynamics.