Hepatic Extraction of Exogenous Insulin and Glucagon in the Dog*

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100

A B ST R A CT The effect of equal (1.1±0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195±15 mg/100 ml) and intraportal glucose infusion (215±11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68±4%) and intraportal glucose administration (65±7%) significantly exceeded that after peripheral intravenous glucose infusion (23±5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6±1.3 U, 4.3±0.6 U after intraportal glucose, and 4.1±0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42±3 to 61±4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion.Received for publication 7 December 1982 and in revised form 3 March 1983.Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged.These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently. INTRODUCTIONThe liver is important in glucose homeostasis. Splanchnic removal of glucose was greater after oral glucose compared with peripheral intravenous administration of glucose (1-6), but the mechanism of this effect is not clearly understood. DeFronzo et al. (5,6) implicated gut factors released after ingestion of glucose but Bergman et al. (7) reported similar hepatic uptake of glucose after intraportal glucose infusion and oral glucose administration. Abumrad et al. (8) also excluded a significant role for gut factors and concluded that both hyperglycemia and hyperinsulinemia were major factors in m...

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 85%

See 1 more Smart Citation

Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs.

Ishida¹,

Chap²,

Chou³

et al. 1983

134

100

“…The liver removes a large fraction, at least 50%, ofthe insulin that impinges upon it (47), as well as a somewhat lesser fraction of glucagon (48). This implies that the diversion of the pancreatic venous drainage to the systemic circulation will at least double the amount ofinsulin entering the periphery in response to a similar metabolic stimulus.…”

Section: Resultsmentioning

confidence: 99%

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

Radziuk

Barron²,

Najm³

et al. 1993

To assess the metabolic consequences of the diversion of the pancreatic venous drainage to the systemic circulation, the pancreaticoduodenal and gastrosplenic veins were anastomosed to the inferior vena cava in nine normal dogs. This procedure maintained the integrity of the entire pancreas while shunting the hormonal output ofthe pancreas to the periphery. The metabolic effects were assessed from the sensitivity to insulin during a euglycemic hyperinsulinemic glucose clamp using an insulin infusion of 800 IAU/kg per min. The studies were controlled by their duplication in seven dogs identically treated but with the pancreatic veins reanastomosed to the portal vein. No differences in systemic insulin levels or insulin sensitivity before and after surgery were seen under these circumstances. After diversion, however, basal insulin levels rose from 4.5±1.0 to 11.5±2.5 gU/ml. Basal glucose metabolic clearance rate (MCR) rose to 3.0±0.4 from 2.0±0.3 ml/kg per min. On insulin infusion, maximal stimulation of MCR within the 2-h infusion period was to 15.2±2.5 ml/kg per min preoperatively and to 7.2±0.8 ml/kg per min after diversion. Using ratios of MCR-to-insulin concentration as an index of insulin sensitivity, it was demonstrated that this index decreased by at least 50% after diversion. These data imply that portal venous drainage of the pancreas is an important factor in the determination of peripheral insulin sensitivity. (J. Clin. Invest. 92:1713-1721

“…end sampling catheters were placed in the portal and hepatic veins of seven mongrel dogs (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) kg; mean weight 22±1.6 kg) according to the methods described by Cherrington et al (10). The portal vein catheter was introduced via the spleen and secured in the portal vein just before its bifurcation into right and left branches in the porta hepatis.…”

Section: Methodsmentioning

confidence: 99%

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

Jaspan¹,

Polonsky²

1982

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