Transpulmonary pyruvate kinetics

2011 ◽  
Vol 301 (3) ◽  
pp. R769-R774 ◽  
Author(s):  
Matthew L. Johnson ◽  
Rajaa Hussien ◽  
Michael A. Horning ◽  
George A. Brooks
Keyword(s):  
Kinetic Studies ◽  
Lung Parenchyma ◽  
Whole Body ◽  
Central Venous ◽  
Epinephrine Infusion ◽  
Major Site ◽  
Intermediary Metabolites ◽  
Pulmonary Capillary ◽  
Unstimulated Control ◽  
Tracer Kinetic

Shuttling of intermediary metabolites, such as pyruvate, contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like pyruvate that are simultaneously taken up from and released into the circulation by organs. However, we understood that during each circulatory passage, the entire cardiac output transits the pulmonary circulation. Therefore, we examined the transpulmonary pyruvate kinetics in an anesthetized rat model during an unstimulated (Con), lactate clamp (LC), and epinephrine infusion (Epi) conditions using a primed-continuous infusion of [U-13C]pyruvate. Compared with Con and Epi stimulation, LC significantly increased mixed central venous ([v̄]) and arterial ([a]) pyruvate concentrations ( P < 0.05). We hypothesized that the lungs, specifically the pulmonary capillary beds are sites of simultaneous production and removal of pyruvate and contributes significantly to whole body carbohydrate intermediary metabolism. Transpulmonary net pyruvate balances were positive during all three conditions, indicating net pyruvate uptake. Net balance was significantly greater during epinephrine stimulation compared with the unstimulated control ( P < 0.05). Tracer-measured pyruvate fractional extraction averaged 42.8 ± 5.8% for all three conditions and was significantly higher during epinephrine stimulation ( P < 0.05) than during either Con or LC conditions, that did not differ from each other. Pyruvate total release (tracer measured uptake − net balance) was significantly higher during epinephrine stimulation (400 ± 100 μg/min) vs. Con (30 ± 20 μg/min) ( P < 0.05). These data are interpreted to mean that significant pyruvate extraction occurs during circulatory transport across lung parenchyma. The extent of pulmonary parenchymal pyruvate extraction predicts high expression of monocarboxylate (lactate/pyruvate) transporters (MCTs) in the tissue. Western blot analysis of whole lung homogenates detected three isoforms, MCT1, MCT2, and MCT4. We conclude that a major site of circulating pyruvate extraction resides with the lungs and that during times of elevated circulating lactate, pyruvate, or epinephrine stimulation, pyruvate extraction is increased.

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.

Changes in regulation of human zinc metabolism with age

1992 ◽  
Vol 263 (5) ◽  
pp. R1162-R1168 ◽  
Author(s):  
M. E. Wastney ◽  
S. Ahmed ◽  
R. I. Henkin
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Zinc Concentration ◽  
Kinetic Studies ◽  
Compartmental Analysis ◽  
Whole Body ◽  
Zinc Metabolism ◽  
Zinc Release ◽  
Urinary Zinc Excretion ◽  
Using Data

To assess changes in zinc metabolism with age, kinetic studies were performed in healthy adults (26 men, 21 women) aged 20-84 yr after a single oral or intravenous bolus of 65Zn. Studies covered two consecutive 9-mo periods while subjects were on a basal dietary intake of approximately 10 mg Zn/day and while taking an additional 100 mg Zn/day orally. Zinc metabolism was analyzed by compartmental analysis using data from plasma, red blood cells, urine, feces, liver, thigh, and whole body [M. E. Wastney, R. L. Aamodt, W. F. Rumble, and R. I. Henkin. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R398-R408, 1986]. Changes in observed and model calculated values of zinc metabolism were assessed on age by regression. During basal state, zinc release from red blood cells decreased with age. During zinc loading, response (defined as change from basal state) of plasma zinc concentration, urinary zinc excretion, and liver zinc increased with age, while response of fraction of zinc taken up by red blood cells decreased with age. In men, response of amount of zinc absorbed increased with age and in women response of fraction of endogenous zinc excreted decreased with age. Four responses that changed with age (urinary excretion, red blood cell exchange, absorption, and endogenous excretion) occurred at previously defined sites of regulation of zinc metabolism. Results show that regulation of zinc metabolism changes with age.

Leucine kinetics from [2H3]- and [13C]leucine infused simultaneously by gut and vein

1991 ◽  
Vol 260 (1) ◽  
pp. E111-E117 ◽  
Author(s):  
R. A. Hoerr ◽  
D. E. Matthews ◽  
D. M. Bier ◽  
V. R. Young
Keyword(s):  
Amino Acid ◽  
Human Subjects ◽  
Kinetic Studies ◽  
Tracer Study ◽  
Experimental Diet ◽  
Fed State ◽  
Leucine Kinetics ◽  
Tracer Kinetic ◽  
Plasma Leucine ◽  
Plasma Compartment

In amino acid tracer kinetic studies of the fed state, ingested amino acid may be taken up during its initial transit through splanchnic tissues and thus not enter the plasma compartment where tracer is infused. To investigate this possibility, adult human subjects received simultaneous intravenous (iv) and intragastric (ig) leucine tracer infusions, first during a postabsorptive (PA) 4-h primed continuous ig infusion of L-[1-13C]-leucine and L-[5,5,5-2H3]leucine iv, followed on a separate day by a fed infusion, in which an ig infusion of a liquid formula was started 2 h before the tracer infusion and continued throughout the tracer study. Subjects were accustomed to a constant experimental diet supplying 1.5 g protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and fed studies, respectively. For the PA study, plasma enrichment for the ig tracer was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/- 0.16 (ig) and 3.02 +/- 0.14 (iv), respectively [not significant (NS)]. For the fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/- 0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and in the fed experiment, 0.76 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

1992 ◽  
Vol 263 (5) ◽  
pp. E850-E855 ◽  
Author(s):  
L. Simonsen ◽  
J. Bulow ◽  
J. Madsen ◽  
N. J. Christensen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Epinephrine Infusion ◽  
Basal Period ◽  
Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

Racial differences in lipid metabolism in women with abdominal obesity

2000 ◽  
Vol 279 (3) ◽  
pp. R944-R950 ◽  
Author(s):  
Susan B. Racette ◽  
Jeffrey F. Horowitz ◽  
Bettina Mittendorfer ◽  
Samuel Klein
Keyword(s):  
Fatty Acid ◽  
Black Women ◽  
Racial Differences ◽  
Abdominal Obesity ◽  
Plasma Insulin ◽  
White Women ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Whole Body ◽  
Epinephrine Infusion

We evaluated palmitate rate of appearance (Ra) in plasma during basal conditions and during a four-stage epinephrine infusion plus pancreatic hormonal clamp in nine white and nine black women with abdominal obesity, who were matched on fat-free mass, total and percent body fat, and waist-to-hip circumference ratio. On the basis of single-slice magnetic resonance imaging analysis, black women had the same amount of subcutaneous abdominal fat but less intra-abdominal fat than white women (68 ± 9 vs. 170 ± 14 cm2, P < 0.05). Basal palmitate Rawas lower in black than in white women (1.95 ± 0.26 vs. 2.88 ± 0.23 μmol · kg fat-free mass−1 · min−1, P < 0.005), even though plasma insulin and catecholamine concentrations were the same in both groups. Palmitate Ra across a physiological range of plasma epinephrine concentrations remained lower in black women, because the increase in palmitate Ra during epinephrine infusion was the same in both groups. We conclude that basal and epinephrine-stimulated palmitate Ra is lower in black than in white women with abdominal obesity. The differences in basal palmitate kinetics are not caused by alterations in plasma insulin or catecholamine concentrations or lipolytic sensitivity to epinephrine. The lower rate of whole body fatty acid flux and smaller intra-abdominal fat mass may have clinical benefits because of the relationship between excessive fatty acid availability and metabolic diseases.

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