Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Abstract

A B S T R A C T Oral glucose (25 g) fed to seven healthy, conscious dogs resulted in an increase in peripheral plasma glucose from 109±3 to 178±10 mg/dl. Concurrently serum insulin increased in the portal vein to levels approximately threefold greater than those in the periphery. Hepatic insulin delivery rose from 10.8±0.7 to 59.0±19.9 mU/min at 60 min, coincident with an increased hepatic insulin extraction from 3.3 to 41.4 mU/min (corresponding to an increase in hepatic extraction from 31±4 to 59±7%), both returning to basal at 3 h. In each animal there was a positive correlation between hepatic insulin delivery and extraction (r = 0.80, P < 0.001 for the seven experiments combined). These changes in hepatic insulin delivery and extraction after glucose feeding were correlated with changes in hepatic glucose metabolism associated with insulin action. As hepatic insulin extraction increased, hepatic glucose output declined, both parameters returning to basal levels by 3 h, indicating a negative correlation between hepatic insulin extraction and hepatic glucose output (r = 0.63, P < 0.001; n = 7).The factors that mediate this marked and rapidly occurring increase in hepatic insulin extraction after oral glucose are unknown, and may include hepatic insulin delivery, glucose levels in the blood supplying the liver, factors related to increased hepatic blood flow, and gut factors released by oral glucose intake. The association of changes in hepatic insulin extraction in vivo with an insulin effect on the liver as measured

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.…”

Effect of Decrease in Both Postprandial Blood Glucose (PBG) and Fasting Blood Glucose (FBG) Levels in Normal Beagle Dogs with Nateglinide Enteric Coated Granules and Immediate Release Tablets

“…Kawamori et al and other researchers have pointed out that plasma insulin concentrations of peripheral veins do not serve as an indicator of insulin secretion from the pancreas based on the results of insulin kinetics and metabolism studies using normal fasting dogs. [14][15][16] In addition, venous plasma insulin concentrations after having passed through the liver have been indicated as being 50% or less of concentrations in the portal vein. 17,18) In other words, the control of blood glucose levels is thought to take place based on insulin concentration in the portal vein and not in the peripheral blood.…”

Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.

“…All subjects were within 10% of ideal body weight. The diabetic patients were insulin-dependent with a disease duration of 9.4±2.3 yr (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. None had clinically significant vascular, renal, eye, or neurological complications.…”

“…The rationale for this approach depends on the fact that the liver is the major site of insulin metabolism, variably extracting -50% of insulin delivered to it (6)(7)(8)(9)(10)(11). C-peptide is Receivedfor publication 25 June 1985 and in revisedform 28 August 1985. cosecreted from the beta cell on an equimolar basis with insulin (12) but does not undergo significant hepatic extraction (13)(14)(15).…”