Evaluation of the isotopic equilibration between lactate and pyruvate

Wolfe, Robert R.; Jahoor, F.; Mizumoto, Hiroshi

doi:10.1152/ajpendo.1988.254.4.e532

Cited by 39 publications

(50 citation statements)

References 7 publications

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“…3, A and B). In vivo, lactate rapidly equilibrates across LDH, making accurate determinations of lactate turnover via tracer infusion more challenging (29). Nevertheless, the individual and overall differences between glycerol and lactate turnover rates identify a substantial shift to a PEPCK-independent gluconeogenic precursor at a rate that can account for a third of EGP (Fig.…”

Section: Pepck-m Deficiency Promotes a Gluconeogenic Substrate Switchmentioning

confidence: 99%

A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis

Stark

Guebre-Egziabher

Zhao

et al. 2014

Journal of Biological Chemistry

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Background: PEPCK-M is generally considered irrelevant for glucose production, although gluconeogenesis has never been characterized in its absence. Results: PEPCK-M loss impaired gluconeogenesis from lactate, lowered plasma glucose, insulin, and triglycerides, reduced hepatic glycogen, and increased glycerol turnover. Conclusion: Approximately a third of gluconeogenesis comes from PEPCK-M.Significance: The nutrient-sensitive PEPCK-M has been overlooked and is potentially important for metabolic diseases such as diabetes.

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Section: Pepck-m Deficiency Promotes a Gluconeogenic Substrate Switchmentioning

confidence: 99%

A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis

Stark

Guebre-Egziabher

Zhao

et al. 2014

Journal of Biological Chemistry

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“…These effects are largely due to monocarboxylate metabolism in the lungs. Hence, assertions that the IEs of lactate and pyruvate are equivalent in mammalian blood following tracer infusion (27) are simply incorrect. In brief, the present results show that the lungs metabolize substrates delivered in the pulmonary artery and, further, that lung metabolism affects metabolite concentrations and isotopic enrichments when tracers are infused into the systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

Transpulmonary lactate shuttle

Johnson

Emhoff

Horning

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Johnson ML, Emhoff CW, Horning MA, Brooks GA. Transpulmonary lactate shuttle. Am J Physiol Regul Integr Comp Physiol 302: R143-R149, 2012. First published October 26, 2011 doi:10.1152/ajpregu.00402.2011.-The shuttling of intermediary metabolites such as lactate through the vasculature contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like lactate that are simultaneously taken up from and released into the circulation by organs, but in each circulatory passage, the entire cardiac output traverses the pulmonary parenchyma. To determine whether transpulmonary lactate shuttling affects whole-body lactate kinetics in vivo, we examined the effects of a lactate load (via lactate clamp, LC) and epinephrine (Epi) stimulation on transpulmonary lactate kinetics in an anesthetized rat model using a primedcontinuous infusion of [U-13 C]lactate. Under all conditions studied, control 1.2 (SD 0.7) (Con), LC 1.9 (SD 2.5), and Epi 1.9 (SD 3.5) mg/min net transpulmonary lactate uptake occurred. 3) conditions, but negative during Epi stimulation, Ϫ25.3% (SD 45.5) when there occurred a transpulmonary production, the conversion of mixed central venous pyruvate to arterial lactate. Further, isotopic equilibration between L and P occurred following tracer lactate infusion, but depending on compartment (v or a) and physiological stimulus, [L]/[P] concentration and isotopic enrichment ratios ranged widely. We conclude that pulmonary arterial-vein concentration difference measurements across the lungs provide an incomplete, and perhaps misleading picture of parenchymal lactate metabolism, especially during epinephrine stimulation. lactate metabolism; lung; pyruvate metabolism; lactate kinetics EARLY RESEARCHERS DEMONSTRATED the ability of the lungs to produce lactate from glucose under fully aerobic conditions (9). Subsequent work identified the lungs as a complex metabolic organ with respect to carbohydrate intermediary metabolism; at times, the lungs were net consumers of lactate, while at other times, such as in patients with acute respiratory distress syndrome, the lungs released lactate on a net basis (1-3, 7, 20). In contrast, many studies were unable to show transpulmonary net uptake or release. Such determinations are complicated due to the high blood flow through the pulmonary circulation in relation to metabolic requirements of lung parenchyma (11, 23). Using [U-14 C]glucose and an isolated perfused rat lung preparation Longmore and Mourning (22) demonstrated that the majority of lactate released during aerobic conditions was derived from glucose. However, upon exposure to hypoxia, lactate production nearly doubled in the preparation, but with only 60% of the lactate produced coming from glucose. When previously hypoxic lungs were reexposed to aerobic conditions, lactate release reverted to production exclusively from glucose. The work of Longmore and Mourning illustrates the diverse metabolic properties of lungs under condit...

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“…Yet, the increased rate of G-6-P neogenesis (4 -8 mol of C6 unit ⅐ kg Ϫ1 ⅐ min Ϫ1 ) exceeded M-HGR (0.9 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), which indicated that the suppression of M-HGR by GPI treatment was associated with abolished net glycogenolysis and also redirected G-6-P flux from glucose release toward other pathway(s), such as glycogen synthesis and glycolysis. In addition, with GPI treatment, there was a shift of net hepatic lactate balance from production to uptake, and with a rapid equilibration between the plasma lactate pool and the intracellular lactate and pyruvate pools (Wolfe et al, 1988), this shift in lactate balance may have reflected a shift from pyruvate generation to pyruvate consumption in the net sense. Intracellular pyruvate is generated by glycolysis and deamination of amino acids mediated by transaminases.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies in dogs and humans have shown that increased delivery of gluconeogenic precursors, such as alanine (Diamond et al, 1988;Wolfe et al, 1988), glycerol (Jahoor et al, 1990), or lactate (Jenssen et al, 1990;Connolly et al, 1993), to the liver has no acute effect on the amount of glucose produced by that organ. Gluconeogenic precursors can alter hepatic glycogen metabolism by exerting regulatory effects on glycogen phosphorylase and synthase in addition to serving as substrates for glycogen synthesis (Youn and Bergman, 1990), of which glucose 6-phosphate (G-6-P), an intermediate at a central cross point between the metabolic pathways of glycogen metabolism and gluconeogenesis, has been shown in studies using isolated hepatocytes to regulate glycogen synthase (Ciudad et al, 1986) and phosphorylase activity within a physiological range (Aiston et al, 2003(Aiston et al, , 2004.…”

Section: Introductionmentioning

confidence: 99%

Impact of a Glycogen Phosphorylase Inhibitor and Metformin on Basal and Glucagon-Stimulated Hepatic Glucose Flux in Conscious Dogs

Torres¹,

Sasaki²,

Donahue³

et al. 2011

J Pharmacol Exp Ther

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The effects of a glycogen phosphorylase inhibitor (GPI) and metformin (MT) on hepatic glucose fluxes (mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) in the presence of basal and 4-fold basal levels of plasma glucagon were investigated in 18-h fasted conscious dogs. Compared with the vehicle treatment, GPI infusion suppressed net hepatic glucose output (NHGO) completely (Ϫ3.8 Ϯ 1.3 versus 9.9 Ϯ 2.8) despite increased glucose 6-phosphate (G-6-P) neogenesis from gluconeogenic precursors (8.1 Ϯ 1.1 versus 5.5 Ϯ 1.1). MT infusion did not alter those parameters. In response to a 4-fold rise in plasma glucagon levels, in the vehicle group, plasma glucose levels were increased 2-fold, and NHGO was increased (43.9 Ϯ 5.7 at 10 min and 22.7 Ϯ 3.4 at steady state) without altering G-6-P neogenesis (3.7 Ϯ 1.5 and 5.5 Ϯ 0.5, respectively). In the GPI group, there was no increase in NHGO due to decreased glucose-6-phosphatase flux associated with reduced G-6-P concentration. A lower G-6-P concentration was the result of increased net glycogenesis without altering G-6-P neogenesis. In the MT group, the increment in NHGO (22.2 Ϯ 4.4 at 10 min and 12.1 Ϯ 3.6 at steady state) was approximately half of that of the vehicle group. The lesser NHGO was associated with reduced glucose-6-phosphatase flux but a rise in G-6-P concentration and only a small incorporation of plasma glucose into glycogen. In conclusion, the inhibition of glycogen phosphorylase a activity decreases basal and glucagon-induced NHGO via redirecting glucose 6-phosphate flux from glucose toward glycogen, and MT decreases glucagon-induced NHGO by inhibiting glucose-6-phospatase flux and thereby reducing glycogen breakdown.

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Evaluation of the isotopic equilibration between lactate and pyruvate

Cited by 39 publications

References 7 publications

A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis

A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis

Transpulmonary lactate shuttle

Impact of a Glycogen Phosphorylase Inhibitor and Metformin on Basal and Glucagon-Stimulated Hepatic Glucose Flux in Conscious Dogs

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