Suppression of Pancreatic Glucagon Secretion by Tolbutamide in Dogs

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Abstract
Conflicting results in the effect of the sulfonylureas upon glucagon release prompted us to investigate the changes of glucagon levels in the pancreaticoduodenal vein of anesthetized dogs. Tolbutamide injection into the femoral vein with or without arginine infusion did not change glucagon levels in the pancreatic vein. The raised level of plasma glucagon in the pancreatic vein during arginine infusion seemed to be suppressed only when tolbutamide was infused into the femoral vein for twenty minutes with a prime dose of 500 mg of the drug. The levels of pancreatic glucagon decreased significantly following the infusion of tolbutamide (10 mg/ min) into the pancreatic artery. In these experiments, the suppression of pancreatic glucagon occurred, when the concentration of tolbutamide in the pancreatic vein exceeded 35 mg/100 ml. Blood glucose fell after tolbutamide injection in dogs in which the pancreas excluding the uncinate process was previously extirpated, in the same manner as in the normal controls. It is concluded that tolbutamide does suppress the pancreatic glucagon release, when the circulating tolbutamide concentration in the pancreas was maintained above 35 mg/ 100 ml. However, the suppression of glucagon in the pancreatic vein does not play an important role in the fall of the blood glucose level following the tolbutamide administration. 1 A part of the paper was presented at the eighth International Diabetes Federation, at Brussels on July 17, 1973.

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