Pentose pathway in human liver.

Magnusson, Inger; Chandramouli, Visvanathan; Schumann, William C.; Kumaran, K; Wahren, John; Landau, Bernard R.

doi:10.1073/pnas.85.13.4682

Cited by 43 publications

(49 citation statements)

References 24 publications

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“…Corrections were made for dilution of water in the blood [31] by the water in which the EDTA was dissolved. Specific activities and 2 H enrichments in urinary glucuronide [25,32] The amount of glucuronide was determined in each 2-h collection [33,34]. The least amounts were in urine collected from 10.00 hours to noon, usually about one-third to one-half that in the other urine samples.…”

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confidence: 99%

Changes in hepatic glycogen cycling during a glucose load in healthy humans

et al. 2005

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Aims/hypothesis: Glycogen cycling, i.e. simultaneous glycogen synthesis and glycogenolysis, affects estimates of glucose fluxes using tracer techniques and may contribute to hyperglycaemia in diabetic conditions. This study presents a new method for quantifying hepatic glycogen cycling in the fed state. Glycogen is synthesised from glucose by the direct and indirect (gluconeogenic) pathways. Since glycogen is also synthesised from glycogen, i.e. glycogen→glucose 1-phosphate→glycogen, that synthesised through the direct and indirect pathways does not account for 100% of glycogen synthesis. The percentage contribution of glycogen cycling to glycogen synthesis then equals the difference between the sum of the percentage contributions of the direct and indirect pathways and 100. Materials and methods: The indirect and direct pathways were measured independently in nine healthy volunteers who had fasted overnight. They ingested 2 H 2 O (5 ml/kg body water) and were infused with [5-3 H] glucose and acetaminophen (paracetamol; 1 g) during hyperglycaemic clamps (7.8 mmol/l) lasting 8 h. The percentage contribution of the indirect pathway was calculated from the ratio of 2 H enrichments at carbon 5 to that at carbon 2, and the contribution of the direct pathway was determined from the 3 H-specific activity, relative to plasma glucose, of the urinary glucuronide excreted between 2 and 4, 4 and 6, and 6 and 8 h. Results: Glucose infusion rates increased (p<0.01) to ∼50 μmol kg −1 min −1 . Plasma insulin and the insulin : glucagon ratio rose ∼3.6-and ∼8.3-fold (p<0.001), respectively. From the difference between 100% and the sum of the direct (2-4 h, 54±6%; 4-6 h, 59±5%; 6-8 h, 63±4%) and indirect (32±3, 38±4, 36±3%) pathways, glycogen cycling was seen to be decreased (p<0.05) from 14±4% (2-4 h) to 4±3% (4-6 h) and 1±3% (6-8 h). Conclusions/interpretation: This method allows measurement of hepatic glycogen cycling in the fed state and demonstrates that glycogen cycling occurs most in the early hours after glucose loading subsequent to a fast.

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Changes in hepatic glycogen cycling during a glucose load in healthy humans

et al. 2005

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“…Urinary acetaminophen ± glucuronide was puri®ed and glucuronide was converted into glucose, as described by Magnusson et al 17 To determine the 13 C abundance of glucuronide, the glucose obtained with this procedure was puri®ed and its 13 C enrichment was measured.…”

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confidence: 99%

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects

et al. 2000

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BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4 h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13 C-galactose infusion, with monitoring of urinary acetaminophen ± glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

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“…We infused into fasted normal subjects, given acetaminophen, [2][3][4][5][6][7][8][9][10][11][12][13][14] C]glycerol, which labels carbons 2 and 5 of glucose-6-P, and [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]lactate, which labels carbons 3 and 4 of glucose-6-P (Fig. 1).…”

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“…This means that during fasting periportal, as compared to perivenous, cells of human liver are exposed to relatively higher glycerol than lactate concentrations. Since a higher capacity for gluconeogenesis is reported to exist in periportal than perivenous cells of animals and for glucuronidation in perivenous than periportal cells (1, 2), we postulated that if carbon-labeled lactate and glycerol were administered to humans and metabolic zonation similarly exists in human liver in vivo, more label from the glycerol would be found in glucose than in a glucuronide relative to label from the lactate.We infused into fasted normal subjects, given acetaminophen, [2][3][4][5][6][7][8][9][10][11][12][13][14] …”

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Gluconeogenesis and Glucuronidation in Liver in Vivo and the Heterogeneity of Hepatocyte Function

Ekberg

Chandramouli

Kumaran

et al. 1995

Journal of Biological Chemistry

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In order to examine metabolic zonation in human liver, [2-14 C]glycerol, which labels carbons 2 and 5 of glucose-6-P, and [1-14 C]lactate, which labels carbons 3 and 4 of glucose-6-P, in the process of gluconeogenesis, were infused intravenously into healthy subjects who ingested acetaminophen and had fasted 36 h. Distributions of 14 C were determined in glucose in blood and in the glucuronic acid moiety of acetaminophen glucuronide excreted in urine. Ratios of 14 C in carbons 2 and 5 to 14 C in carbons 3 and 4 were significantly higher in blood glucose than in glucuronide. Since glucose and glucuronic acid are formed from glucose-6-P in liver without randomization of carbon, the differences in the ratios indicate that the pool of glucose-6-P in liver is not homogeneous. The glucuronide sampled glucose-6-P with more label from lactate than glycerol compared to the glucose-6-P sampled by the glucose. The apparent explanation is the greater decrease in glycerol compared with lactate concentration as blood streams from the periportal to the perivenous zones of the liver lobule. Glucuronidation is then expressed in humans relatively more in the perivenous than periportal zones and gluconeogenesis from glycerol more in the periportal than perivenous zones.Hepatocytes from the periportal and perivenous zones of livers of animals have been found by in vitro techniques to have differing metabolic capacities (1, 2). In gluconeogenesis, glucose-6-P formed from gluconeogenic substrates is hydrolyzed to glucose. In glucuronidation, glucuronic acid from UDP-glucuronic acid is conjugated. The UDP-glucuronic acid is formed from glucose-6-P with glucose-1-P and UDP-glucose as intermediates. Thus, both glucose and glucuronic acid are formed from glucose-6-P with carbon skeletons unchanged.In humans fasted for 12 h and 60 h, the concentration of glycerol, but not lactate, is much lower in hepatic vein than arterial blood (3-5). This means that during fasting periportal, as compared to perivenous, cells of human liver are exposed to relatively higher glycerol than lactate concentrations. Since a higher capacity for gluconeogenesis is reported to exist in periportal than perivenous cells of animals and for glucuronidation in perivenous than periportal cells (1, 2), we postulated that if carbon-labeled lactate and glycerol were administered to humans and metabolic zonation similarly exists in human liver in vivo, more label from the glycerol would be found in glucose than in a glucuronide relative to label from the lactate.We infused into fasted normal subjects, given acetaminophen, [2][3][4][5][6][7][8][9][10][11][12][13][14]

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Pentose pathway in human liver.

Cited by 43 publications

References 24 publications

Changes in hepatic glycogen cycling during a glucose load in healthy humans

Changes in hepatic glycogen cycling during a glucose load in healthy humans

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects

Gluconeogenesis and Glucuronidation in Liver in Vivo and the Heterogeneity of Hepatocyte Function

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