Hepatic Extraction of Exogenous Insulin and Glucagon in the Dog*

Abstract

Insulin and glucagon were infused simultaneously into anesthetized mongrel dogs to assess whether exogenous hormone administration would affect the hepatic extraction of insulin (EI) and/or glucagon (EGG). During an equilibration period and a subsequent control period, saline was infused into the portal circulation via the caudal pancreaticoduodenal artery. Blood samples for insulin, glucagon, and glucose were obtained frequently during the 30-min control period from the portal vein, left common hepatic vein and femoral artery. Plasma flows were measured in the portal vein and hepatic artery. Then the saline infusion was replaced by insulin (0.035 U/min) and glucagon (0.32 .mu.g/min) which were infused together over a period of 50 min. This caused an 8-fold increase in the portal vein insulin concentration and a 15-fold increase in the corresponding glucagon concentration. E1 decreased significantly during the infusion from a control value of 63 .+-. 5% to a nadir of 18 .+-. 8%. It returned to control values again during the 30-min postinfusion period. Control EGG (5 .+-. 3%) was significantly smaller than the corresponding E1, and showed no clearcut changes during the infusion period except for a transient initial increase. When the infusion was stopped EGG fell promptly and became negative (nadir obtained 5 min after the end of the infusion, -29 .+-. 5%). The hepatic glucose output increased from 56 .+-. 10 mg/min to 278 .+-. 36 mg/min in response to the infusion, and returned to the basal level again during the postinfusion period. Portal vein molar insulin:glucagon ratio (I/GG) changed in the opposite direction compared to hepatic glucose output, and decreased from a control value of 8.4 .+-. 2.0 to a level of approximately 4 during the hormone infusion. When the infusion ceased, portal vein I/GG tended to rebound. In contrast, femoral arterial I/GG (control 2.5 .+-. 0.8) did not change during the infusion, but reached a level significantly above the control at the end of the postinfusion period (6.9 .+-. 1.6). The portal vein, but not peripheral I/GG measurements, reflected hepatic carbohydrate metabolism in anesthetized dogs infused with insulin and glucagon, probably because of different hepatic extraction patterns for the 2 hormones.