Impact of Glucose Ingestion on Hepatic and Peripheral Glucose Metabolism in Man: An Analysis Based on Simultaneous Use of the Forearm and Double Isotope Techniques*

Abstract

The metabolic response to glucose ingestion was studied in 10 normal men (aged 21-23 yr) by the simultaneous application of the forearm and double isotope techniques. The latter consisted of a primed constant infusion of [3-3H]glucose, followed by the administration of an oral glucose load (mean +/- SE, 90.7 +/- 0.7 g) containing [1-14C]glucose. Most (80.6 +/- 8.1%) of the ingested glucose appeared systemically within 270 min, suggesting that initial splanchnic glucose extraction accounted for 19.4 +/- 3.1% (17.7 +/- 2.8 g) of the oral load. Basal hepatic glucose output (2.22 +/- 0.12 mg/kg X min) was reduced (P less than 0.005) within 30 min after glucose loading and remained suppressed throughout the study; its mean reduction from 0-270 min was 54.9 +/- 9.9%, thereby accounting for the conservation of 26.5 +/- 4.9 g glucose. Suprabasal glucose appearance from 0-270 min was 46.6 +/- 4.3 g. Forearm glucose uptake rose 8.5-fold to 0.664 +/- 0.083 mg/100 ml forearm X min at 45 min, but basal forearm oxygen uptake (6.1 +/- 0.4 mumol/100 ml forearm X min) did not change. The increment in glucose disappearance from 0-270 min was 46.4 +/- 3.8 g, of which increased glucose uptake by muscle, determined from the forearm glucose uptake data, accounted for 37.7 +/- 5.1 g (81%). If uptake of the remaining 8.7 g was shared equally by the liver and peripheral tissues, the splanchnic bed and periphery would account, respectively, for 47.1 g (52%) and 43.5 g (48%) of the ingested load. We conclude that splanchnic and peripheral tissues contribute almost equally to the total homeostatic response; in kinetic terms, decreased hepatic glucose output and increased glucose uptake (splanchnic plus peripheral) constitute 29% and 71% of the total response, respectively; restoration of basal glucose kinetics after glucose ingestion requires more than 270 min; and increased peripheral oxygen uptake is not the mechanism of glucose-induced thermogenesis which, instead, may reflect increased splanchnic oxygen consumption.

Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis

“…The ingested glucose accounted for an average of 77.7 Ϯ 2.4% of the circulating glucose during this interval, a value similar to the ϳ75% found by Kelley et al (34) and Féry et al (24) under comparable experimental conditions. Although the rate of appearance of the ingested glucose was still above zero at 270 min, this probably represented ingested glucose initially incorporated into hepatic glycogen (54) rather than ongoing intestinal absorption (33,34). Therefore, with the assumption of complete absorption of the ingested glucose, net splanchnic sequestration would have amounted to 22.0 Ϯ 2.2 g (29.3 Ϯ 2.9% of the ingested load).…”

“…Limb balance measurements indicate that skeletal muscle is the predominant site for this peripheral glucose disposal, being responsible for about one-fourth of the ingested carbohydrate (5, 26, 33-35, 37, 38, 44). The fate of the remaining 40% of the ingested carbohydrate is less clear.In addition to tissue uptake of ingested carbohydrate, another important factor for postprandial glucose homeostasis is suppression of the release of glucose endogenously produced by gluconeogenesis and breakdown of stored glycogen (18,33,44). Until recently, this was thought to occur almost exclusively in the liver (51).…”

“…In addition to tissue uptake of ingested carbohydrate, another important factor for postprandial glucose homeostasis is suppression of the release of glucose endogenously produced by gluconeogenesis and breakdown of stored glycogen (18,33,44). Until recently, this was thought to occur almost exclusively in the liver (51).…”

Glycogen: its mode of formation and contribution to hepatic glucose output in postabsorptive humans

“…Regarding this assumption, the studies of Radziuk [14] and Jackson et al [25] indicate that absorption of ingested glucose would be complete by 4.5-5 h. Furthermore, the data of Jackson et al [25], Mitrakou et al [10], and Kelley et al [24] indicate that at least 80 % of the ingested glucose would have been removed from plasma within 5 h of its ingestion. Given a half-life in plasma of 44.4 min for glucose [25], it can be calculated that less than 0.15 % of the last ingested glucose load would not have been removed from plasma. Thus, the assumption that all of the [6-3H] glucose in plasma at the time of our measurements originated solely from breakdown of glycogen seems to be justified.…”

Portal infusion of a selective serotonin reuptake inhibitor enhances hepatic glucose disposal in conscious dogs

“…National Institutes of Health guidelines for the care and use of laboratory animals were followed in all respects, and the housing facility met the standards of, and is regularly inspected by, the United States Department of Agriculture. The 42-h-fast was used because it reduces hepatic glycogen concentrations to a stable minimum (15) and because it causes the liver to become a net consumer rather than a producer of lactate [resembling the metabolic state of the overnightfasted human (19,20)]. …”