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

Stingl, Harald; Chandramouli, Visvanathan; Schumann, William C.; Brehm, Attila; Nowotny, Peter; Waldhäusl, W.; Landau, Bernard R.; Roden, Michael

doi:10.1007/s00125-005-0099-x

Cited by 19 publications

(21 citation statements)

References 57 publications

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“…Assuming that ϳ20 grams of glucose was taken up by the liver and converted to UDPG, then the contribution of UDPG flux from galactose could be as high as 10.4/30.4 ϭ 34%. However, similar G2/body water ratios (ϳ0.83) were also found during a hyperglycemic clamp, where glucose is the only carbohydrate source for hepatic glycogen synthesis and UDPG synthesis from galactose is negligible (28). These observations suggest that incomplete G6P-F6P exchange could also contribute to a reduced G2 enrichment.…”

Section: Discussionsupporting

confidence: 62%

“…With [1-13 C]glucose, glycogen cycling dilutes the label at the level of UDPG resulting in an underestimate of the direct pathway contribution to glycogen synthesis. This is also true for the H]glucose tracer (28). Finally, transaldolase activity exchanges the bottom triose unit of F6P with glyceraldehyde-3-phosphate.…”

Section: Discussionmentioning

confidence: 68%

“…In a study of healthy subjects that were given [1-13 C]glucose by infusion after a breakfast meal, direct pathway estimates of 60 -70% were reported (4). From the study of Stingl et al (28), where dilution of infused [5-3 H]glucose in glucuronide versus plasma glucose was measured, the direct pathway accounted for 54 -63% of glycogen synthesis in healthy subjects under hyperglycemic clamp conditions. Our direct pathway estimate of 59% for healthy subjects is more closely matched to those measurements where the glucose tracer was infused rather than where it was ingested with the meal.…”

Section: Discussionmentioning

confidence: 99%

“…With [1-13 C] or [5-3 H]glucose, galactose metabolism will dilute the enrichment or specific activity of UDPG, resulting in an underestimate of direct pathway contribution. Glycogen cycling will also modify glucuronide 2 H-enrichment distribution in positions 5 and 2 (28). Inflow of unlabeled hexose units from glycogen hydrolysis results in a systematic dilution of 2 H-enrichment in all sites except for position 2.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, transaldolase activity exchanges the bottom triose unit of F6P with glyceraldehyde-3-phosphate. This provides an additional mechanism for enriching hydrogen 5 from 2 H 2 O or for depleting the specific activity of [5-3 H]hexose, therefore with both tracers, the direct pathway contribution is underestimated (28). With [1-13 C]glucose, this process does not influence glucuronide C1 enrichment but may slightly increase the enrichment of C6, resulting in a minor underestimation of the direct pathway fraction.…”

Section: Discussionmentioning

confidence: 99%

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Noninvasive Analysis of Hepatic Glycogen Kinetics Before and After Breakfast with Deuterated Water and Acetaminophen

et al. 2006

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The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of 2 H 2 O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body water (G5/body water) was significantly higher in type 1 diabetic patients compared with control subjects, indicating a reduced contribution of glycogenolysis to glucose production (38 ؎ 3 vs. 46 ؎ 2%). Following breakfast, G5/body water was significantly higher in type 1 diabetic patients, indicating a smaller direct pathway contribution to glycogen synthesis (47 ؎ 2 vs. 59 ؎ 2%). Glucuronide hydrogen 2 enrichment (G2) was equivalent to body water during fasting (G2/body water 0.94 ؎ 0.03 and 1.02 ؎ 0.06 for control and type 1 diabetic subjects, respectively) but was significantly lower after breakfast (G2/body water 0.78 ؎ 0.03 and 0.82 ؎ 0.05 for control and type 1 diabetic subjects, respectively). The reduced postprandial G2 levels reflect incomplete glucose-6-phosphate-fructose-6-phosphate exchange or glycogen synthesis from dietary galactose. Unlike current measurements of human hepatic glycogen metabolism, the 2 H 2 O/acetaminophen assay does not require specialized on-site clinical equipment or personnel. Diabetes

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Noninvasive Analysis of Hepatic Glycogen Kinetics Before and After Breakfast with Deuterated Water and Acetaminophen

et al. 2006

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Current literature in diabetes

2006

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author

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Quantification of hepatic transaldolase exchange activity and its effects on tracer measurements of indirect pathway flux in humans

Jones¹,

Garcia²,

Barosa³

et al. 2008

Magnetic Resonance in Med

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Exchange of hepatic glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate via transaldolase modifies hepatic G6P enrichment from glucose or gluconeogenic tracers. Transaldolase exchange was quantified in five healthy, fed subjects following an oral bolus of [1,2,3-13 C 3 ]glycerol (25-30 mg/kg) and paracetamol (10 -12 mg/kg). 13 Hepatic glucose-6-phosphate (G6P) lies at the metabolic crossroads of hepatic glucose and glycogen metabolism. Under fasting conditions when the liver is a net producer of glucose, hepatic G6P is generated by the hydrolysis of glycogen and from gluconeogenesis and is then converted to glucose via G6P. Under fed conditions there is net hepatic glycogen synthesis from both glucose and from gluconeogenic precursors. These metabolic pathways converge at G6P and the hexose carbon skeletons are then incorporated into glycogen via glucose-1-phosphate and UDP-glucose. The gluconeogenic contribution to G6P synthesis is modified in a variety of human diseases, including insulin-and noninsulin-dependent diabetes, cirrhosis, and malaria (1-4). Therefore, quantifying the fraction of G6P derived from gluconeogenesis is a key parameter for defining hepatic carbohydrate metabolism under these and other pathophysiological conditions. In humans, several different tracer methods have been developed for quantifying the contribution of gluconeogenesis to hepatic G6P flux. Hepatic G6P enrichment from these tracers can be quantified noninvasively by analysis of urinary glucuronide enrichment (5-7).Implicit in all measurements of hepatic gluconeogenesis using labeled gluconeogenic substrates is the assumption that G6P molecules derived from non-gluconeogenic precursors (i.e., glycogenolysis) are not labeled with the tracer. 1 Likewise, when labeled glucose is used to determine the contribution of direct and indirect pathways of hepatic glycogen synthesis under fed conditions, dilution of the glucose tracer at the level of hepatic G6P is assumed to be entirely due to gluconeogenic G6P production.The possibility that transaldolase (TA) exchange could invalidate these assumptions was recognized by Landau and co-workers (8 -10). TA catalyzes the exchange between the glyceraldehyde-3-phosphate (GA3P) moiety (i.e., carbons 4, 5, and 6) of fructose-6-phosphate (F6P) and free GA3P in many tissues (11)(12)(13). This exchange is independent of oxidative pentose phosphate pathway (PPP) flux, hence tissues that have relatively low oxidative PPP utilization of G6P, such as liver, may nevertheless have significant TA exchange activity (13). Since G6P and F6P are in rapid exchange, G6P molecules derived from glucose or glycogen are exposed to TA activity. With gluconeogenic tracers that label GA3P, the effect of TA exchange is to transfer the label to G6P molecules derived from glucose or glycogen. Hence, the gluconeogenic contribution is overestimated relative to the contribution from

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

Cited by 19 publications

References 57 publications

Noninvasive Analysis of Hepatic Glycogen Kinetics Before and After Breakfast with Deuterated Water and Acetaminophen

Noninvasive Analysis of Hepatic Glycogen Kinetics Before and After Breakfast with Deuterated Water and Acetaminophen

Current literature in diabetes

Quantification of hepatic transaldolase exchange activity and its effects on tracer measurements of indirect pathway flux in humans

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