Effect of Intraduodenal Glucose Administration on Hepatic Extraction of Insulin in the Anesthetized Dog

Abstract

A B S T R A C T Extraction of insulin by the liver after administration of glucose in the duodenum has been studied in fourteen anesthetized dogs. Plasma insulin and glucose were measured in the portal vein hepatic vein and hepatic artery. During the control period 40 ±3% of the approximately 11 mU of insulin presented to the liver/min was removed during a single transhepatic passage. Within 5 min after glucose administration, the amount of insulin reaching the liver increased significantly. In some animals this increase preceded any significant increase in the glucose concentration of the femoral artery. After glucose administration, hepatic extraction of insulin remained unchanged in five animals and rose significantly in nine. In five of the latter animals, the increase may have been more apparent than real due to nonrepresentative sampling of hepatic venous blood. However, for the whole group of animals, comparison of arterial insulin levels with the amount of insulin delivered to the liver suggested a transient increase in insulin extraction between 5 and 50 min after glucose administration. In no animal was there a decrease in the proportion of insulin extracted by the liver after glucose administration. The results indicate that the extraction process is not saturable at physiological insulin levels. Prior to glucose administration, net hepatic glucose output averaged between 30 and 40 mg/min. After glucose administration, the liver began to take up glucose and there was a significant correlation between hepatic glucose uptake and the amount of insulin reaching the liver. However, since the amount of glucose presented to the liver also increased, it is not established that the insulin was responsible for the change in hepatic carbohydrate metabolism.The data demonstrate an increase in the absolute amount of insulin extracted by the liver after glucose administration and an important role for the liver in regulating peripheral insulin concentrations.

Estimation of pancreatic IRI output rate and its relation to glucose tolerance in normal anaesthetized dogs

“…The values represent the function of the whole organ (not only of one of its vascular regions). The estimated amounts of IRI output for anaesthetized dogs are comparable to the calculations by indirect methods of other authors [11,20,44 [33] -2.5 mU/min (15 kg). Some of the values referred to were converted or they were taken from figures.…”

Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test

“…Reasons for this may include the fact that C-peptide and insulin antibodies have no cross-reaction [20] and that it does not undergo significant hepatic extraction [21,22]. Note, the liver is the major site of insulin metabolism, variably extracting ~50% of insulin delivered to it [23][24][25]. It has therefore been suggested that peripheral C-peptide levels more accurately reflect pancreatic insulin secretion rates than do peripheral insulin levels.…”

Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man.

“…Insulin secreted from the B-cell reaches the liver, where about 50% of insulin is extracted and modulated, according to Madison and Kaplan (1958), Kaden et al (1973) and Mondon et al (1975). In contrast, as far as C-peptide is concerned, only a small part is handled in the liver and most of C-peptide is excreted from the kidney (Katz and Rubenstein 1973;Sherwin et al 1976;Rabkin et al 1978).…”