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

Abstract

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...

Insulin Regulates Retinol Dehydrogenase Expression and All-trans-retinoic Acid Biosynthesis through FoxO1

“…Glucose delivery by the portal vein combined with insulin, and an as yet unidentified neuronal signal, increases net hepatic glucose uptake compared with peripheral delivery, with a concomitant impact on insulin-regulated processes (52,53). A comparison of oral glucose dosing to infusion via the portal vein revealed similar enhancement in hepatic glucose uptake relative to peripheral presentation, which excludes a contribution from a gut-secreted factor, such as Glp-1 (54).…”

Self-regulatory depletion in dogs: Insulin release is not necessary for the replenishment of persistence

“…For the following 2 min, the experimenter sat quietly while the dog was allowed to digest the beverage. This 2-min duration was sufficient for digestion, insulin response, and for the orally administered glucose to be transported into the brain (Betz, Gilboe, Yudilevich, and Drewes, 1973;Ishida et al, 1983).…”

The metabolic clearance of glucose: measurement and meaning

“…One method for calculating the rate of production of glucose involves measuring the rate of glucose influx into the liver (portal vein and hepatic artery), and subtracting from this the rate of effiux from the liver [3][4][5].…”