First-pass hepatic retention of glucose had previously been measured indirectly from the appearance of ingested labelled glucose into the systemic circulation. To determine the accuracy of the procedure, results obtained by this indirect method were compared with those of direct measurement of hepatic retention of labelled glucose given by instantaneous injection into the portal vein. In the rat, the indirect procedure gave a value of 13.7 +/- 2.3%. In the direct method, [14C]glucose was injected intraportally together with [3H]sucrose as a marker of extracellular distribution. Hepatic content of both labels was maximal immediately after administration; the content of sucrose fell to basal values by 15 s, indicating that the injected bolus had passed through the liver; the content of [14C]glucose continued to fall for 90 s. The difference in tissue retention between glucose and sucrose, representing intracellular glucose, was constant from 90 to 180 s, and indicated a first-pass retention of 13 +/- 0.7%. Thus the indirect procedure gives a reliable estimate of hepatic uptake and retention of glucose. Comparison of the time courses of hepatic content of [14C]glucose, [2-3H]glucose and [3H]sucrose indicated that 50% of portal-vein glucose enters the hepatic cells; subsequently 15% traverses the glucose/glucose 6-phosphate futile cycle, 22% is released without undergoing metabolic change and 13% is retained for metabolic purposes.

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