Comparison of Hepatic Extraction of Insulin and Glucagon in Conscious and Anesthetized Dogs*

Abstract

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10–20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 ± 10 and 44 ± 7 μU/ml, respectively) and glucagon (247 ± 37 and 219 ± 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 ± 62 vs. 294 ± 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious nimals, the basal hepatic extractions of insulin (42 ± 6 vs. 39 ± 6%, respectively) and glucagon (12 ± 7 vs. 7 ± 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg·min) and glucagon (4 ng/kg·min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exgenous hormones was significantly greater in the anesthetized animals.