Demonstration of gastric glucagon hypersecretion in insulin-deprived alloxan-diabetic dogs

The contribution of the gastric fundus to the hyperglucagonemia of poorly controlled diabetes was studied in insulin-deprived alloxan-diabetic dogs by simultaneously measuring plasma glucagon in the venous effluents of the fundus and the pancreas, and in inferior vena caval plasma. In the basal state, mean glucagon averaged 411 ± 45 pg./ml. in the gastric vein and 941 ± 161 in the pancreaticoduodenal vein; both values were significantly above the vena caval level of 281 ± 35 (p < 0.01). Intravenous arginine infusion caused gastric vein glucagon to rise from 335 ± 91 pg./ml. before the infusion to 1,180 ± 432 after 1.5 minutes; this was significantly above the mean vena caval glucagon concentration which reached a peak of only 352 ± 74 (p < 0.01 to < 0.05). Intragastric instillation of arginine was followed by a doubling of gastric vein glucagon within 10 minutes, and the increases in the gastric vein were significantly greater than in the peripheral plasma at several points. The infusion of insulin at a rate of 0.0015 u./kg./min. rapidly lowered glucagon in the gastric and pancreaticoduodenal veins, abolishing the gradient across the stomach and reducing the transpancreatic gradient. The studies raise the possibility that extrapancreatic glucagon may contribute to the hyperglucagonemia of insulin deficiency.