Measurement of pyruvate and lactate kinetics across the hindlimb and gut of anesthetized dogs

1994 ◽  
Vol 267 (1) ◽  
pp. E174-E182 ◽  
Author(s):  
D. L. Chinkes ◽  
X. J. Zhang ◽  
J. A. Romijn ◽  
Y. Sakurai ◽  
R. R. Wolfe
Keyword(s):  
Free Water ◽  
Whole Body ◽  
Transmembrane Transport ◽  
New Model ◽  
Lactate Kinetics ◽  
Stable Isotopic ◽  
Anesthetized Dogs ◽  
Flow Through ◽  
Lactate And Pyruvate

We have developed a new model to quantify regional pyruvate and lactate transmembrane transport, shunting, exchange, production, and oxidation in vivo. The method is based on the systemic continuous infusion of pyruvate or lactate stable isotopic carbon tracers and the measurement of pyruvate and lactate enrichment and concentration in the artery and vein of that region (e.g., leg or gut), the pyruvate and lactate enrichment of intracellular free water in the tissue as measured by biopsy, and the rate of blood flow through the tissue. The purpose of the experiment was to measure the pyruvate and lactate kinetics in leg muscle and gut in anesthetized dogs (n = 6). The transmembrane transport and degree of shunting of pyruvate and lactate were comparable in muscle and gut. When modified for substrate inflow, interconversion between pyruvate and lactate took place at a rate twice as fast in muscle as in the gut, and production and oxidation of pyruvate was approximately 50% greater in muscle than in the gut. Thus our new model enables quantitation of many aspects of lactate and pyruvate kinetics. We conclude that in anesthetized animals the muscle is the tissue most responsible for whole body peripheral pyruvate and lactate kinetics.

Quantification of in vitro and in vivo energy metabolism of the gastrointestinal tract of fed or fasted sheep

1993 ◽  
Vol 73 (4) ◽  
pp. 855-868 ◽  
Author(s):  
J. M. Kelly ◽  
B. G. Southorn ◽  
C. E. Kelly ◽  
L. P. Milligan ◽  
B. W. McBride
Keyword(s):  
Blood Flow ◽  
Gastrointestinal Tract ◽  
Portal Blood Flow ◽  
Whole Body ◽  
Hepatic Portal Vein ◽  
Flow Through ◽  
Hepatic Portal ◽  
Ouabain Inhibition

The effect of level of nutrition on in vitro and in vivo O2 consumption by the gastrointestinal tract in four nonlactating, nonpregnant ewes catheterized in the anterior mesenteric vein, hepatic portal vein and mesenteric artery with duodenal cannulae was investigated. Animals were fed a pelleted ration at maintenance (M) or twice maintenance (2M) or fasted (F) subsequent to the M measurement. Duodenal in vitro O2, ouabain-sensitive O2 (OSO2) and cycloheximide-sensitive O2 (CSO2) consumption was determined polarographically using a YSI O2 monitor; whole-gut O2 consumption was determined as (arterio-venous difference of O2 concentration) × (blood flow through the PV). Whole-body O2 consumption was determined using indirect calorimetry. Ewes fed 2M exhibited higher (P < 0.10) whole-body O2 consumption than either M or F ewes. Ewes fed M and 2M had higher (P < 0.10) duodenal in vitro O2 and ouabain-insensitive O2 (OIO2) consumption than F ewes. Hepatic portal blood flow was directly proportional to level of intake (P < 0.10): it was lowest for F ewes (81.0 L h−1), intermediate for M ewes (97.7 L h−1) and highest for 2M ewes (122.5 L h−1). Ouabain inhibition of O2 consumption by portal-drained viscera (PDV) was highest in M ewes and lowest in 2M ewes (P < 0.10). CSO2 consumption by the entire PDV was not affected by level of intake, corresponding to no change in OIO2 consumption by the PDV. As a proportion of whole-body O2 consumption, total O2, OSO2 and cycloheximide-insensitive O2 consumption by the PDV was higher in F ewes than in 2M ewes (P < 0.10). Fasted ewes expended a greater proportion of whole-body O2 consumption on gastrointestinal energetics than did 2M ewes. Key words: Sheep, gastrointestinal oxygen consumption, sodium–potassium ATPase, protein synthesis

Respiratory quotients of human kidney in vivo

1963 ◽  
Vol 18 (4) ◽  
pp. 815-817 ◽  
Author(s):  
Earl S. Barker ◽  
Archer P. Crosley ◽  
John K. Clark
Keyword(s):  
Human Subjects ◽  
Human Kidney ◽  
Mean Value ◽  
Whole Body ◽  
Mean Values ◽  
Anesthetized Dogs ◽  
The Mean ◽  
Urine Formation ◽  
Analytical Errors

Renal respiratory quotient (RQ) has been calculated from data collected in unanesthetized human subjects. In contrast to RQ recently reported on anesthetized dogs, these data do not indicate a mean value greater than 1. Under control conditions in 24 subjects, renal RQ calculated without special corrections averaged 0.88. Correcting for differences in blood flow between renal artery and vein due to urine formation the mean was 0.73, with 95% confidence limits 0.49–0.97. With alkaline urines an additional correction for urinary excretion of CO2 is advised. Excluding procedures known to alkalinize the urine, RQ values were similar in 46 observations after a variety of experimental procedures. Since both numerator and denominator of the ratio involve small differences between large values, small analytical errors can produce large changes indistinguishable from physiologic variation. Therefore mean values rather than individual observations are stressed. While such values in our data appear similar to RQ for other organs and the whole body, they do not preclude considerable anaerobic metabolism. Submitted on August 9, 1962

Evaluation of the isotopic equilibration between lactate and pyruvate

1988 ◽  
Vol 254 (4) ◽  
pp. E532-E535 ◽  
Author(s):  
R. R. Wolfe ◽  
F. Jahoor ◽  
H. Miyoshi
Keyword(s):  
Steady State ◽  
Metabolic Flux ◽  
Isotopic Exchange ◽  
Whole Body ◽  
Isotopic Enrichment ◽  
Isotopic Tracer ◽  
Anesthetized Dogs ◽  
Isotopic Equilibration ◽  
Lactate And Pyruvate ◽  
Kinetics Of

When an isotopic tracer is infused for the purpose of determining the rate of turnover or oxidation of a substrate, it is assumed that the resulting isotopic enrichment by the tracer will reflect the kinetics of only the pool of interest. However, this may not be the case when carbon-labeled lactate is infused, since rapid isotopic exchange with the intracellular pyruvate and alanine pools could potentially occur. Therefore we have determined the extent of isotopic exchange occurring during the infusion of [3-13C]lactate into six anesthetized dogs. In the steady state, pyruvate enrichment was 91 +/- 2.2% (means +/- SE) of the lactate enrichment, and alanine enrichment was 81 +/- 3.3% of the pyruvate enrichment and 72 +/- 2.6% of the lactate enrichment. In contrast, when [3-13C]alanine was infused (n = 2), pyruvate (and lactate) enrichment was 9.9% of the alanine enrichment. We therefore conclude that there is rapid isotopic equilibration between lactate and pyruvate but that interaction with alanine reflects the true metabolic flux rates, rather than isotopic exchange. Consequently, lactate kinetics, as traditionally determined, more accurately reflect whole body pyruvate kinetics.

Specific localization of α-ketoglutarate uptake to dog kidney and liver in vivo

1965 ◽  
Vol 208 (1) ◽  
pp. 24-37 ◽  
Author(s):  
Burnell H. Selleck ◽  
Julius J. Cohen
Keyword(s):  
Steady State ◽  
Membrane Transport ◽  
Extracellular Fluid ◽  
Whole Body ◽  
Net Uptake ◽  
Dog Kidney ◽  
Liver And Kidney ◽  
Specific Localization ◽  
Lactate And Pyruvate

Net uptake of infused α-ketoglutarate (α-KG) occurs almost exclusively in dog kidney and liver; in contrast, lactate or pyruvate uptake occurs in most organs. The following observations support these conclusions: 1) in measurements of steady-state net renal and whole-body uptake of α-KG, lactate, and pyruvate, kidney takes up ≈50% of the total α-KG utilized as compared to lactate (≈15%) or pyruvate (≈17%); 2) liver and kidney extract more α-KG from blood than do the lower extremities, brain, intestine, or heart; 3) exclusion of either the kidneys or the liver, or both, from the circulation shows that these organs are the major determinants of the rate of α-KG clearance from blood. The virtual volume of α-KG distribution in the hepatectomized, nephrectomized dog is approximately that of extracellular fluid. The selective uptake of α-KG is compared to the membrane transport of p-aminohippurate (PAH) by these two organs. It is suggested that the general, and perhaps primary, function of the PAH transport system is to move specific metabolites to sites of dissimilation in liver and kidney.

Mechanism of Ionic Diffusion in Dense Bentonite

1988 ◽  
Vol 127 ◽  
Author(s):  
S.C.H. Cheung ◽  
M. N. Gray
Keyword(s):  
Interstitial Water ◽  
Particle Surface ◽  
Free Water ◽  
Clay Particle ◽  
Ionic Diffusion ◽  
Interstitial Free ◽  
New Model ◽  
Compacted Bentonite ◽  
Flow Through ◽  
Through Diffusion

ABSTRACTA new model based on ionic diffusion in surface (bound) and interstitial (free) water in compacted bentonite systems has been developed. The model is supported by data obtained from flow-through diffusion experiments using Cs+, I- and Cl-. The results show that diffusion depends on the charge of the diffusing species: cations are attracted to the clay particle surface, but are not immobilized, whereas anions are repelled from the clay particle surface. Cations diffuse through both surface and interstitial water, and anions diffuse mainly through interstitial water. The clay structure has been found to affect the diffusion of cations and anions.

scholarly journals Transpulmonary lactate shuttle

2012 ◽  
Vol 302 (1) ◽  
pp. R143-R149 ◽  
Author(s):  
Matthew L. Johnson ◽  
Chi-An W. Emhoff ◽  
Michael A. Horning ◽  
George A. Brooks
Keyword(s):  
Kinetic Studies ◽  
Whole Body ◽  
Central Venous ◽  
Intermediary Metabolites ◽  
Lactate Shuttle ◽  
Concentration Difference ◽  
Lactate Kinetics ◽  
Clamp Condition ◽  
Pulmonary Parenchyma

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 primed-continuous infusion of [U-13C]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. Compared with Con, a lactate load via LC significantly increased mixed central venous ([v̄]) [1.9 mM (SD 0.5) vs. 4.7 (SD 0.4)] and arterial ([a]) [1.6 mM (SD 0.4) vs. 4.1 (SD 0.6)] lactate concentrations ( P < 0.05). Transpulmonary lactate gradient ([v̄] − [a]) was highest during the lactate clamp condition [0.6 mM (SD 0.7)] and lowest during Epi [0.2 mM (SD 0.5)] stimulation ( P < 0.05). Tracer measured lactate fractional extractions were similar for control, 16.6% (SD 15.3), and lactate clamp, 8.2% (SD 15.3) conditions, but negative during Epi stimulation, −25.3% (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 (v̄ 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.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

scholarly journals Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
KyeongJin Kim ◽  
Jin Ku Kang ◽  
Young Hoon Jung ◽  
Sang Bae Lee ◽  
Raffaela Rametta ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Whole Body ◽  
Acid Oxidation ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Ph Domain ◽  
Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

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