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PubMed1981

The determination of lactate turnover in vivo with 3H- and 14C-labelled lactate. The significance of sites of tracer administration and sampling.

L-[3-3H,U-14C]Lactate was administered to starved rats either as a bolus or by continuous infusion. Tracer administration was performed two ways: injection into the vena cava and sampling from the aorta (V-A mode), or injection into the aorta and sampling from the vena cava (A-VC mode). The specific-radioactivity curves after infusion or injection differed markedly with the two procedures. However, the specific radioactivities of 14C-labelled glucose derived from [U-14C]lactate were similar in the two modes. The apparent turnover rates of lactate calculated from the 3H specific-radioactivity curves in the V-A mode were about half those obtained from the 3H specific-radioactivity curves in the A-VC mode. The apparent contribution of lactate carbon to glucose carbon calculated from specific-radioactivity curves of the A-VC mode was greater than that obtained from the V-A mode. The apparent recycling of lactate carbon calculated from the specific radioactivities for [U-14C]- and [3-3H]-lactate was greater in the A-VC mode than the V-A mode. [U-14C] Glucose was administered in the two modes, but in contrast with lactate the specific radioactivities were only slightly different. An analysis to account for these observations is presented. It is shown that the two modes represent sampling from different pools of lactate. The significance of sites of tracer administration and sampling for the interpretation of tracer kinetics of compounds present in intracellular and extracellular spaces, and with a high turnover rate, is discussed. We propose that for such compounds, including lactate, alanine and glycerol, the widely used V-A mode leads to a marked underestimate of replacement, mass and carbon recycling, and that the A-VC mode is the preferred method for the assessment of these parameters.

Animals↗
PubMed1988

Regulation of lactate uptake and lactate production in liver from 48-h-starved rats: effects of pH, flow and glucose concentration.

1. The effects of medium glucose concentration (0-20 mmol/l) and flow (100-33% of normal) on lactate uptake at low lactate concentration were studied in perfused livers from 48-h-starved rats with perfusate pH values of 7.4 and 6.8. 2. Lactate uptake was independent of glucose concentration in the range 5-10 mmol/l, but was slightly inhibited with time at 20 mmol/l glucose. This pattern was independent of perfusate pH. 3. At both pH values lactate uptake decreased proportionally with flow, and at low flow lactate was produced by the livers. The effect of flow was greatest at pH 7.4 where a net lactate production was found at 48% of normal flow, whereas at pH 6.8 lactate production was not seen until the flow was reduced to 33% of normal. 4. When glucose was omitted from the perfusate lactate production ceased at both pH values. 5. The effect of low pH on lactate uptake and production in liver probably reflects inhibition of glycolysis by low pH.

Animals↗
PubMed1992

Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood?

We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation.

Animals↗
PubMed1998

Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate.

We examined the effects of increasing a known lactate transporter protein, monocarboxylate transporter 1 (MCT1), on lactate extrusion from human skeletal muscle during exercise. Before and after short-term bicycle ergometry training [2 h/day, 7 days at 65% maximal oxygen consumption (VO2max)], subjects (n = 7) completed a continuous bicycle ergometer ride at 30% VO2max (15 min), 60% VO2max (15 min), and 75% VO2max (15 min). Muscle biopsy samples (vastus lateralis) and arterial and femoral venous blood samples were obtained before exercise and at the end of each workload. After 7 days of training the MCT1 content in muscle was increased (+18%; P < 0.05). The concentrations of both muscle lactate and femoral venous lactate were reduced during exercise (P < 0.05) that was performed after training. High correlations were observed between muscle lactate and venous lactate before training (r = 0.92, P < 0.05) and after training (r = 0.85, P < 0.05), but the slopes of the regression lines between these variables differed markedly. Before training, the slope was 0.12 +/- 0.01 mM lactate.mmol lactate-1.kg muscle dry wt-1, and this was increased by 33% after training to 0.18 +/- 0.02 mM lactate.mmol lactate-1.kg muscle dry wt-1. This indicated that after training the femoral venous lactate concentrations were increased for a given amount of muscle lactate. These results suggest that lactate extrusion from exercising muscles is increased after training, and this may be associated with the increase in skeletal muscle MCT1.

Adult↗
PubMed2003

Gene expression of resistin in adipose tissue and mammary gland of lactating and non-lactating cows.

Resistin has been suggested to induce insulin resistance in obesity and to inhibit adipocyte differentiation. In lactating cows, glucose uptake in the mammary gland is a rate-limiting step in milk synthesis, and to supply glucose to the mammary gland, insulin resistance increases. We examined the expression of the resistin gene by real-time PCR of cDNA in the adipose tIssue and mammary gland of lactating and non-lactating cows. Lactation induced a significant increase of resistin expression in adipose tIssue compared with that in the dry period, and decreased resistin expression in the mammary gland. There were no significant differences in the expression of insulin responsive glucose transporter (GLUT4) mRNA between the adipose tIssue of lactating and non-lactating cows, and GLUT4 mRNA was not detected in the mammary gland. The plasma insulin concentration was lower in lactating cows than in non-lactating cows. These results indicate that the pattern of resistin expression in peripheral tIssues is changed in association with milk production. The increase of resistin expression and maintenance of a lower level of plasma insulin concentration may decrease glucose availability by increasing insulin resistance in adipose tIssue. Additionally, our results suggest that the decrease of resistin expression in the mammary gland may influence on the insulin-dependent glucose uptake in mammary epithelial cells during lactation.

Adipose Tissue↗
PubMed2001

The regression of unsuckled mammary glands during lactation in sows: the influence of lactation stage, dietary nutrients, and litter size.

During lactation in the sow, mammary glands that are not regularly suckled undergo regression. This study characterizes the regression of unsuckled mammary glands and how that regression is affected by dietary nutrients and litter size. Sixty-nine primiparous sows were fed one of four diets containing combinations of two protein levels (32 or 65 g lysine/d) and two energy levels (12 or 17.5 Mcal ME/d) during lactation. Litter size was adjusted to 10. Sows were killed on d 0, 5, 10, 14, 21, or 28 of lactation. In another experiment, twenty-eight primiparous sows were allotted to have different litter sizes and were killed on d 21 of lactation. The day before slaughter, teat order of each litter was observed. After death, mammary glands were removed and dissected. Skin and extraneous fat pads were removed from the mammary glands and individual glands were separated. Each gland was weighed, cut in half to measure cross-sectional area, and ground for chemical analysis. The amounts of dry tissue, protein, fat, ash, and DNA were measured. Only glands observed to be unsuckled were included in the results. Regression of unsuckled mammary glands occurred rapidly during the first 7 to 10 d of lactation, as indicated by a decline in wet weight, dry weight, protein, fat, DNA, and cross-sectional area. The rate of regression was slowed after the early lactation period. The rate of regression of unsuckled glands was affected by dietary nutrient levels. Dietary energy level affected (P < 0.05) the decline in wet and dry weights, protein, fat and DNA content, and cross-sectional area, whereas dietary protein level affected (P < 0.05) the decline in dry weight and fat content. At d 5 of lactation, the wet weight of unsuckled mammary glands in sows fed the high-energy high-protein diet was 91% greater (P < 0.05) than in sows fed the low-energy low-protein diet. Effects of litter size on size and composition of unsuckled glands were not significant by d 21 of lactation. Unsuckled mammary glands regress rapidly during early lactation, and the rate of regression is affected by dietary nutrient intake.

Animal Feed↗
PubMed2004

Deconstructing milk yield and composition during lactation using biologically based lactation models.

A recently developed biological model of lactation described changes in daily milk yield throughout lactation as the result of 3 processes, secretory cell differentiation, cell death, and secretion rate per cell. This paper extends the model to describe the production of milk components (fat, protein, lactose, and water) throughout lactation by replacing milk secretion rate of the original model with the secretion rates of the four components. The milk component model approach was used to examine the relationship between milk yield and the major determinants of its production, using the secretion of milk components throughout lactation. Newly derived models were tested on 461 lactations from a single Holstein herd and used to estimate variability of secretion rates throughout lactation. Because the pattern of cell numbers throughout lactation is not precisely known, an alternative pattern of cell numbers was modeled and the concomitant change in secretion rates outlined. Fat secretion rate was the most variable, as measured by its weekly coefficient of variation throughout lactation. Secretion rates of lactose and water were nearly constant throughout lactation and highly correlated (0.94). Fat and protein secretion rates also were well correlated (0.53). The known biochemistry of milk component production related well to the secretion rate observations derived from the model. Lactose secretion rate and numbers of active secretory cells primarily determined daily milk yield.

Animals↗
PubMed1991

Total lactational response to added fat during early lactation.

The theory that feeding cows additional fat during early lactation will result in greater total lactational production and improved reproductive efficiency was evaluated using 305-d lactational data from 94 cows fed control diets and 96 cows fed additional dietary fat during wk 4 through 16 postpartum. Added fat in diets was supplied by oilseeds, either soybeans or sunflowers, in previously reported studies. Milk yield during wk 4 through 16 postpartum was 2.8% higher for cows fed added fat. Total lactational yield was increased 3.6% for cows fed additional fat in early lactation; 71% of the additional milk production occurred after discontinuing the feeding of additional fat. Percentages of milk fat and protein were lower when cows were fed added fat and remained lower for the remainder of the lactation. Days to first breeding, days open, and services per conception were not reduced by feeding added fat during early lactation. Milk production and persistency for the entire lactation were increased by feeding additional fat during early lactation, but changes in reproductive efficiency were not detected.

Animals↗
PubMed1977

[Blood picture in lactate acidosis. Part 2: acid-base equilibrium and lactate].

A differentiation between lactate emia (lactic acid emia) and lactate acidosis (lactic acidosis) is made. The normal value for blood lactate concentration is 1-2 mmol/1. The term lactate emia is used for lactate values between 2-6 mmol/1. The limiting value for the diagnosis of lactate acidosis should be more than 7-8 mmol/1 for the blood lactate concentration. Furthermore the different buffer mechanisms are evaluated in respect to their influence on the pH of the blood and to lactate metabolism. Especially the mechanism of respiratory compensation for metabolic acidosis is discussed. It is stated that for the diagnosis of lactate acidosis the blood-pH and the bicarbonate concentration should be measured.

Acid-Base Equilibrium↗
PubMed1991

Lactate analyzer with continuous blood sampling for monitoring blood lactate during physical exercise.

To monitor changes in the concentration of blood lactate during physical exercise, we used an automated lactate analyzer based on an electro-enzymatic method with continuous blood sampling through a catheter. The lactate concentration was measured every 2 min; between measurements, the instrument was calibrated with a lactate standard. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere with the measurements. The lactate concentrations in blood samples from apparently healthy subjects before and after exercise correlated well (r = 0.993) with results by the conventional enzymatic method. We measured the blood lactate concentrations in nine apparently healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. Thus, the lactate analyzer is suitable for monitoring changes in blood lactate concentrations during exercise.

Autoanalysis↗