SEARCH · Search PubMed

Results for “LACTATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources

PubMed1998

Effects of noradrenaline and flow on lactate uptake in the perfused rat hindlimb.

Skeletal muscle can release or take up lactate depending on the lactate concentration gradient across the cell membrane. In the perfused rat hindlimb without arterial lactate, both noradrenaline (NA) infusion and increased flow promote lactate release and oxygen consumption (VO2). However, it is unclear whether NA or increased flow rate have similar effects on lactate uptake. The present study compares these effects in the rat hindlimb perfused at a basal flow rate of 0.33 mL min-1 g-1 and 25 degrees C in the presence of added arterial lactate. When 10 mmol L-1 L-(+)-lactate was added to the arterial perfusate, lactate was taken up (16 +/- 1.0 mumol g-1 h-1, n = 13) by the hindlimb with a 35% higher VO2 than that without added lactate. Doubling perfusion flow rate enhanced lactate uptake and VO2 by 120% and 40%, respectively. Glucose uptake was also increased (by 253%) with increased flow. Infusion of NA increased perfusion pressure, VO2 and glucose uptake similarly to those induced by increased flow rate. However, lactate uptake was inhibited by NA. This inhibition was not altered by the beta-adrenergic antagonist propranolol. Vasopressin also showed similar effects to NA to decrease lactate uptake associated with increased VO2 and vasoconstriction. These data indicate that in the presence of a high arterial lactate concentration, NA has opposite effects from increased flow rate on skeletal muscle lactate uptake although both have similar effects on lactate release in the absence of arterial lactate. Inhibition of lactate uptake may relate to the vasoconstrictive action of NA.

Adrenergic beta-Antagonists↗

PubMed2003

Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients.

OBJECTIVE: To evaluate the prognostic value of lactate clearance and lactate production in severely ill septic patients with normal or mildly elevated blood lactate concentration. DESIGN Prospective, observational study. SETTING: Nineteen-bed mixed medicosurgical intensive care unit. PATIENTS: Fifty-six patients with severe sepsis and blood lactate concentration <3 mmol/L. MEASUREMENTS AND MAIN RESULTS: Lactate metabolism was evaluated in all patients. Lactate clearance was measured by modeling the change in arterial blood lactate over time induced by an infusion of 1 mmol/kg sodium lactate for 15 mins. Lactate production was calculated as the product of lactate clearance times the blood lactate concentration before the infusion. Outcome was taken to be mortality at 28 days after the beginning of the septic episode. A logistic regression model taking into account different risk factors was constructed. Among the 56 patients, 17 (30.3%) died before the 28th day. Basal blood lactate concentration was not different between survivors and nonsurvivors, whereas lactate clearance and production were higher in survivors (0.86 +/- 0.32 vs. 0.58 +/- 0.18 L/hr/kg, p < .005, and 1.19 +/- 0.63 vs. 0.89 +/- 0.24 mmol/hr/kg, p = .055, respectively). An increase in blood lactate 45 mins after the end of the lactate infusion (Deltalact-T60) > or = 0.6 mmol/L was predictive of 28-day mortality with 53% sensitivity and 90% specificity. Multivariate analysis showed that only three factors were independently and significantly correlated with 28-day mortality: presence of more than two organ failures (odds ratio, 27; p = .04), age >70 yrs (odds ratio, 5.7; p = .032), and Deltalact-T60 > or =0.6 mmol/L (odds ratio, 14.2; p = .042). CONCLUSION: Low lactate clearance in severely ill septic patients with normal or mildly elevated blood lactate is predictive of poor outcome independently of other known risk factors such as age and number of organ failures.

Age Distribution↗

PubMed1965

[Metabolism Of C(14)-Lactate By Fasciola Hepatica And Eurytrema Pancreaticum]

The adult trematode, Fasciola hepatica and Eurytrema pancreaticum, employed in this experiment were obtained from the cattle slaughtered at the local abbatoir. The worms were selected and washed several times in normal sterilized saline solution. Each ten of intact F. hepatica and about thirty to fifty of E. pancreaticum were incubated in 50 cc volume of special incubation flasks with incubation medium consisting of 50 cc of Krebs-Ringer phosohate buffer (pH 7.4). The incubation medium was added C(14)-lactate and non-radioactive carrier Na-lactate so as to contain lactate concentration of 32 mg per cent. The worms were allowed to incubate for 3 hours in the Dubnoff metabolic shaking incubator at 38 degrees C. After incubation period, respiratory CO2 samples from central wall of incubation flask were analysed for total CO2 production rate and their specific activity of respiratory CO2. The lactate uptake rate was determined by analyzing the the difference between lactate concentration in a medium before and after the incubation period, and the pyruvate appearance rate was dertermined by analyzing the pyruvate concentration in a medium after incubation. The glycogen samples isolated from worms were analyzed for the tissue concentration and their radioactivities in order to determine the turnover rate of glycogen pool. Radioactivities of these serise of experiment were counted by an endwindow Geiger-Muller counter as an infinitely thin samples. The quantative analysis of C(14)-lactate utilized by F. hepatica and E. pancreaticum were summerized and compared as following. In F. hepatica the lactate uptake rate was a mean value of 1.04 +/- 0.15 micro M/hr/g of wet wt. and pyruvate apperance rate was a mean value of 0.132 +/- 0.005 micro M/hr/g of wet wt. The total CO2 production rate by the flukes averaged 13.82 +/- 0.75 micro M/hr/g of wet wt. The relative specific activities of respiratory CO2 R.S.A(CO2) showed a mean value of 9.93 +/- 0.62 per cent. The rate of CO2 production derived from medium C(14)-lactate was a mean of 1.38 +/- 0.13 micro M/hr/g of wet wt. Therefore the averge value of 55.27 +/- 5.78 per cent (R.L.D(CO2)) and 15.35 +/- 1.90 per cent (R.L.D(pyr)) of lactate was oxidized into respiratory CO2 and pyruvate respectively. On the other hand, in E. pancreaticum the lactate uptake rate was a mean value of 0.61 +/- 0.18 micro M/hr/g of wet wt, and pyruvate appearance rate was a mean of 0.023 +/- 0.001 micro M/hr/g of wet wt. The total CO2 production rate by the E. pancreaticum averaged 4.29 +/- 0.85 micro M/hr/g of wet wt. The relative specific activity of respiratory CO2 (R.S.A(CO2)) showed a mean value of 9.20 +/- 0.34 per cent. Thus, a mean value of 9.20 per cent of total CO2 production rates was originated from C14-lactate in a medium, therefore the rate of CO2 production derived from medium C(14)-lactate was a mean value of 0.40 +/- 0.10 micro M/hr/g of wet wt. The average value of 23.93 +/- 7.11 per cent(R.L.D(CO2)) and 3.86 +/- 0.45 per cent(R.L.D(pyr)) of lactate was oxidized into respiratory CO2 and pyruvate respectively. The tissue concentration of glycogen in F. hepatica was a mean of 2.63 per cent/g of wet wt, while in E. pancreaticum was a mean of 4.06 per cent/g of wet wt. The turnover rate of glycogen pool in F. hepatica yielded a value of 0.073 +/- 0.008 micro M/hr/g of wet wt whereas in E. pancreaticum yielded only a mean of 0.006 +/- 0.002 mg/hr/g of wet wt. Therefore, the half time (t(2/1)) of glycogen turnover, which is the time interval required to replace the half of glycogen pool with medium C(14)-lactate, gave value of a mean of 10.73+/-0.76 days in F. hepatica. However, incorporation of C(14)-lactate into glycogen was negligible in the E. pancreaticum. Theses data impressed that the carbohydrate such as lactate may play a role of major part of their oxidative metabolism in F. hepatica, whereas minor part of lactate participates in the oxidative metabolism in E. pancreaticum.

Journal Article↗

PubMed2006

Screening of foetal distress by assessment of umbilical cord lactate.

PURPOSE OF INVESTIGATION: Studies on umbilical cord blood for determination of lactate indicate that high levels seem to be correlated to foetal metabolism for anaerobic glycolysis taking place in oxygen-deprived tissues of the foetus. These findings may be of particular-deprived clinical importance when foetal distress or foetal hypoxemia is caused by perinatal events. METHODS: The maternal and foetal heart rates, acid-base values measured and the outcome of 94 pregnancies complicated by intrapartum foetal asphyxia have been reviewed, and the maternal and foetal acid-base and lactate levels during the course of labour and at delivery were studied in patients with evidence of metabolic acidosis. Lactate concentrations were measured during labour and at delivery in blood samples obtained from the foetal presenting part and from the umbilical cord with the use of a rapid electrochemical technique. The foetuses were evaluated by means of the Apgar score, intrapartum cardiotocography, observation of the presence of meconium stained amniotic fluid, and clinical features of distress at birth. RESULTS: Evidence of clinical foetal distress was not related to the severity of the asphyxia. An increased lactate level was found in asphyctic infants and a clear correlation between lactic acidosis and foetal distress was documented. Low Apgar scores were observed in infants with moderate or severe asphyxia at delivery. Scalp lactate correlated significantly with umbilical artery lactate, but not with 1-min or 5-min Apgar scores. The lactate concentration was higher in cases of instrumental delivery compared to spontaneous delivery. No perfect correlation was found between lactate level and neonatal outcome but there were not a significant number of neonates with immediate complications. The rate of forceps delivery in the distress group was significantly higher than that of the healthy foetuses, so spontaneous labour was less frequently associated with foetal distress than instrumental delivery. In the distress group, severe variable decelerations were generally recorded in the second stage of labour. The incidence of neonatal Apgar score < or = 7 in neonates with abnormal baseline foetal heart rate (FHR) was higher than in those with severe variable decelerations, mild variable decelerations, and transient tachycardia. Duration of the active second stage of labour was significantly with the presence of foetal lactate at the time of crowning of the foetal head and the presence of lactate in umbilical arterial and vein blood at delivery. Expulsion time > or = 45 minutes, compared with shorter active second stage, and acidaemia at birth implied larger arterial-venous lactate differences. The presence of foetal lactate at crowning was also significantly associated with the level of umbilical arterial-venous lactate difference. CONCLUSION: Lactate and pH values provide the best parameters to distinguish between asphyctic and normal newborns, with lactate having the most discriminating power. The prospective value of the discrimination functions derived from lactate and pH data is good when the foetuses are allocated into normal parameters but poor when an attempt is made to allocate the foetuses into pathologic ones, with a high false-negative rate. However, the discriminating ability is improved when pathologic foetuses are included into one single abnormal group. These results confirm the potential use of rapid foetal blood lactate measurements for the early diagnosis of intrapartum foetal distress.

Acidosis, Lactic↗

PubMedDate not supplied

Futile cycling of lactate through the plasma membrane of C6 glioma cells as detected by (13C, 2H) NMR.

We report a novel ((13)C, (2)H) nuclear magnetic resonance (NMR) procedure to investigate lactate recycling through the monocarboxylate transporter of the plasma membrane of cells in culture. C6 glioma cells were incubated with [3-(13)C]lactate in Krebs-Henseleit Buffer containing 50% (2)H(2)O (vol/vol) for up to 30 hr. (13)C NMR analysis of aliquots progressively taken from the medium, showed: (1) a linearly decreasing singlet at approximately 20.85 parts per million (ppm; -0.119 micromol/mg protein/hr) derived from the methyl carbon of [3-(13)C]lactate; and (2) an exponentially increasing shifted singlet at approximately 20.74 ppm (0.227 micromol/ mg protein/hr) from the methyl carbon of [3-(13)C, 2-(2)H]lactate. The shifted singlet appears because during its transit through the cytosol, [3-(13)C]lactate generates [3-(13)C, 2-(2)H]lactate in the lactate dehydrogenase (LDH) equilibrium, which may return to the incubation medium through the reversible monocarboxylate carrier. The methyl group of [3-(13)C, 2-(2)H]lactate is shifted -0.11 ppm with respect to that of [3-(13)C]lactate, making it possible to distinguish between both molecules by (13)C NMR. During incubations with 2.5 mM [1-(13)C]glucose and 3.98 mM [U-(13)C(3)]lactate or with 2.5 mM [1-(13)C]glucose and 3.93 mM [2-(13)C]pyruvate, C2-deuterated lactate was produced only from [1-(13)C]glucose or [U-(13)C(3)]lactate, revealing that this deuteration process is redox sensitive. When [1-(13)C]glucose and [U-(13)C(3)]lactate were used as substrates, no significant [3-(13)C]lactate production from [1-(13)C]glucose was detected, suggesting that glycolytic lactate production may be stopped under the high lactate concentrations prevailing under mild hypoxic or ischemic episodes or during cerebral activation.

Animals↗

PubMed1995

Colonic lactate metabolism and D-lactic acidosis.

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal < 0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal < 0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not have D-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100 + 150 g of ingested lactose increased D-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increased D-lactate to 13.6 +/- 3.5 mmol/liter in feces, but never increased D-lactate in plasma or urine. The in vitro fermentation of glucose in fecal homogenates increased DL-lactate, which disappeared after complete metabolization of the glucose. L-Lactate was converted to D-lactate and vice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite for D-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion that D-lactate is not metabolized and hence accumulates is probably not valid.

Acidosis, Lactic↗

PubMed1992

Skeletal muscle is a major site of lactate uptake and release during hyperinsulinemia.

During conditions of increased glucose disposal, plasma lactate concentrations increase due to an increase in plasma lactate appearance. The tissue sites of the elevated lactate production are controversial. Although skeletal muscle would be a logical source of this lactate, studies using the limb net balance technique have failed to demonstrate a major change in net lactate output when plasma glucose disposal is increased. Because the limb balance technique underestimates production of a substrate when the limb not only produces but also consumes that substrate, we infused 3-14C-lactate basally and during a hyperinsulinemic euglycemic clamp in seven normal volunteers to determine plasma lactate appearance, forearm lactate fractional extraction, and forearm lactate uptake and release. After 3 hours of hyperinsulinemia, glucose and lactate turnovers increased from basal values of 11.8 +/- 0.13 and 12.2 +/- 0.59 to 32.6 +/- 3.4 and 16.5 +/- 1.07 mumol/(min.kg), accompanied by an increase in plasma lactate from 0.88 +/- 0.07 to 1.16 +/- 0.09 mmol/L (P less than .05). Forearm lactate extraction increased from 27% +/- 2% to 38% +/- 2% (P less than .001), resulting in an increase in forearm lactate uptake from 0.65 +/- 0.09 to 1.18 +/- 0.08 mumol/(min.100 mL tissue) (P less than .001). Although forearm lactate net output decreased during hyperinsulinemia, forearm lactate production increased from 1.04 +/- 0.12 basally to 1.69 +/- 0.13 mumol/(min.100 mL). When forearm data was extrapolated to whole body, muscle could account for 41% +/- 4% of systemic lactate appearance basally and 45% +/- 4% during hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1993

Effect of insulin and glucose load on bile lactate secretion by the isolated rat liver. Role of hepatic parenchyma heterogeneity.

Parenchymal heterogeneity in lactate disposal by perivenous and periportal hepatocytes is believed to be an important factor affecting the overall lactate metabolism by the liver. The aim of this work was to investigate the possibility of the existence of a different role of both acinar zones 1 and 3 in lactate secretion into bile. The effect of insulin and glucose load was also studied using isolated in situ rat liver preparations. Perfusions with erythrocyte-free Krebs-Henseleit solutions were carried out in intact livers and after restricted damage of zone 1 or zone 3 by digitonin administration as a bolus through the portal or the hepatic vein, respectively. In intact livers lactate concentrations in bile were similar to those found in the perfusate. In both compartments lactate concentrations were observed to increase over 90 min of perfusion. During this time, bile lactate output increased from 5 to 8 nmol/min per g liver with no significant effect on bile flow. Replacement of perfusate by a fresh lactate-free one at 60 min failed to induce any reduction in lactate concentration in bile samples collected during the following 30 min which suggests the absence of easy equilibration of biliary lactate with the sinusoidal compartment. Insulin administration (bolus: 100 mU/100 g body weight, plus portal infusion: 5 mU/min per 100 g body weight) was found to markedly enhance bile lactate concentrations (+110%) and output (+139%). On the contrary, glucose load was found to have no effect on lactate output into bile. No significant difference in the increase in bile lactate output was observed during 90 min perfusion with either 0, 5, 10, 15, 25 or 35 mM initial glucose concentrations. After restricted damage of acinar zone 1 or 3, insulin-induced bile lactate secretion was significantly reduced. This effect was not different regardless the damaged acinar zone. In summary these results suggest that insulin plays an important role in the control of the output of lactate into bile and that the existence of acinar heterogeneity in this function seems unlikely. Moreover the quantitative contribution of bile lactate to overall lactate handling by the liver and to bile formation seems very low.

Animals↗

PubMed2007

Serum leptin and insulin levels in lactating protein-restricted rats: implications for energy balance.

The present study analysed the effect of protein restriction on serum insulin and leptin levels and their relationship with energy balance during lactation. Four groups of rats received isocaloric diets containing 170 g protein/kg or 60 g protein/kg from pregnancy until the 14th day of lactation: control non-lactating, control lactating (both fed a control diet), low-protein non-lactating and low-protein lactating. Energy intake, body composition, energy balance, serum insulin and leptin concentrations and the relationship between these hormones and several factors related to obesity were analysed. Low-protein-intake lactating rats exhibited hypoinsulinaemia, hyperleptinaemia, hypophagia and decreased energy expenditure compared with control lactating rats. The protein level in the carcasses was lower in the low-protein lactating group than in the control lactating group, resulting in a higher fat content in the first group compared with the latter. Body fat correlated inversely with serum insulin and positively with serum leptin level. There was a significant negative correlation between serum leptin and energy intake, and a positive relationship between energy intake and serum insulin level in lactating rats and in the combined data from both groups. Energy expenditure was correlated positively with serum insulin and negatively with serum leptin in lactating rats and when data from control non-lactating and lactating rats were pooled. Lactating rats submitted to protein restriction, compared with lactating control rats, showed that maternal reserves were preserved owing to less severe negative energy balance. This metabolic adaptation was obtained, at least in part, by hypoinsulinaemia that resulted in increased insulin sensitivity favouring enhanced fat deposition, hyperleptinaemia and hypophagia.

Animal Nutritional Physiological Phenomena↗

PubMed1984

The influence of renal function on lactate and glucose metabolism.

The relationship of lactate metabolism to renal function was studied in the isolated perfused rat kidney. A new radioisotopic method has been developed that enables the simultaneous measurement of lactate production and consumption in the presence of physiological concentrations of both lactate and glucose. In kidneys from fed rats, when glucose was absent, lactate production was only 12 mumol/h per g dry wt, and in kidneys from starved rats there was no lactate production, indicating that neither the phosphoenolpyruvate/pyruvate substrate cycle nor other analogous cycles for the recycling of lactate carbon are operating in the intact kidney cortex. Lactate production from glucose occurred at a high rate, at the same time as lactate consumption, demonstrating that lactate recycling between renal cortex and medulla can occur in the intact kidney. Lactate production from glucose correlated with glomerular filtration rate (P less than 0.001), urine flow rate (P less than 0.01) and sodium reabsorption (P less than 0.05). There was significant basal lactate production at zero glomerular filtration rate. Lactate consumption was not correlated with any renal function. When Na+ reabsorption was inhibited with the diuretic frusemide, or when filtration was entirely prevented (the 'non'-filtering kidney'), lactate production was decreased by 39% and 50% respectively. Basal lactate production determined in this way was the same as that calculated above by linear regression. Prevention of filtration, but not the addition of frusemide, significantly inhibited lactate consumption. It is concluded that glycolysis is required for medullary Na+ transport, and that some different transport function(s) require lactate oxidation.

Animals↗

PubMed1992

Myocardial lactate extraction and release at rest and during heavy exercise in healthy men.

The relationship between myocardial lactate extraction and blood lactate concentration and the possibility that simultaneous uptake and release of lactate occur in the normal human heart was investigated by measuring arterial-coronary sinus differences of lactate and of labelled lactate during infusion of 14C lactate in 13 healthy young male volunteers. Measurements were done at rest, during increased cardiac work with unaltered arterial lactate concentration achieved by atrial pacing and during increased cardiac work and increased arterial lactate concentration achieved by supine cycle ergometer exercise. There was on no occasion a significant difference in 14C lactate specific activity between arterial and coronary sinus blood, i.e. no significant admixture of non-labelled lactate occurred in the coronary sinus indicating that on no occasion was there any sign of lactate release. The myocardial extraction of lactate seemed to be a linear function of arterial lactate concentration. During exercise with an arterial lactate concentration of 6 mmol l-1 and above, lactate could have covered approximately 75-100% of the oxidative metabolism. Thus, during short-term heavy work myocardial lactate extraction dominates over other substrates (mainly free fatty acids and glucose) taken up by the heart, and used for oxidation by the heart muscle cells.

Adult↗

PubMed2002

Leg and arm lactate and substrate kinetics during exercise.

To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed by 10 min of double poling and diagonal stride at 72-76% maximal O(2) uptake. A high lactate appearance rate (R(a), 184 +/- 17 micromol x kg(-1) x min(-1)) but a low arterial lactate concentration ( approximately 2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate release by the arm of approximately 2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was approximately 45% at rest and approximately 95% of disappearance rate and limb lactate uptake, respectively. Limb lactate kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level despite high lactate R(a) during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying that lactate uptake and subsequent oxidation are also dependent on an elevated metabolic rate. The relative contribution of whole body and limb lactate oxidation is between 20 and 30% of total carbohydrate oxidation at rest and during exercise under the various conditions. Skeletal muscle can change its limb net glucose uptake severalfold within minutes, causing a redistribution of the available glucose because whole body glucose turnover was unchanged.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1992

Metabolic fate of lactate after vigorous activity in the leopard frog, Rana pipiens.

Although the ability of isolated frog muscle to synthesize glycogen from lactate has long been known, it has never been demonstrated that this metabolic activity occurs in the intact frog. Our results clearly indicate that lactate glycogenesis in frog muscle occurs to a significant extent in vivo. During recovery from strenuous exercise, most of the lactate accumulated by frogs seems to be recycled into muscle glycogen because the lactate that disappears during recovery could account nearly stoichiometrically for the glycogen that accumulates in muscle. Furthermore, the decrease in body lactate and the increase in muscle glycogen follow corresponding time courses, suggesting a precursor-product relationship between lactate and glycogen. During recovery from intense exercise, hepatectomized and normal frogs have nearly identical extents of lactate elimination and glycogen synthesis. This suggests that muscle is the main tissue responsible for the recycling of lactate into muscle glycogen and that liver plays a negligible role in lactate disposal. The negligible hepatic contribution to lactate recycling results in part from the liver's incapacity to produce glucose from lactate. In support of this proposition, we show that frog liver perfused in vitro is unable to incorporate any detectable labeled lactate into glucose despite its excellent physiological integrity. Changes in dietary status, training state, season at which the experiments were done, exercise status, and composition of the perfusion media (pH, hormonal composition, physiological saline vs. culture medium) did not give rise to lactate gluconeogenesis. Because frog liver contains all the regulatory enzymes of the gluconeogenic pathway, its inability to synthesize glucose from lactate is not due to an absence of pyruvate carboxylase. A limited ability for lactate uptake may explain why frog liver cannot produce glucose from lactate.

Animals↗

PubMed1990

Enhanced efficiency of lactate removal after endurance training.

The effects of endurance training (running 1 h/day at 40 m/min, 10% grade) on net lactate removal at various lactate concentrations were assessed in resting rats by use of constant exogenous lactate infusion (0, 69.3, 123.6, and 175.0 mumol.kg-1.min-1). No consistent difference in resting lactate concentrations, 1.17 +/- 0.09 mM, was observed between control and trained animals with no exogenous infusion of lactate. With increasing lactate infusion rates, control animals demonstrated a twofold greater increase in blood lactate concentration (range 1.2-11.4 mM) compared with trained animals (range 1.0-5.5 mM). This response resulted from a more rapid rise in net lactate removal with changes in blood lactate concentration for trained animals. The estimated maximal reaction velocity for net lactate removal in trained animals was 19% lower than in control animals; however, the Michaelis-Menten constant was greater than 66% lower in trained animals (4 mM) compared with controls (12 mM). Control animals also demonstrated a twofold greater increase in lactate concentration as a function of the tracer-estimated lactate turnover. The ratio of 14CO2 yield to lactate specific activity as a function of total tracer removal was not significantly different between groups, suggesting that the relative contributions of oxidation and gluconeogenesis to lactate removal were similar for both groups. At blood concentrations greater than 1 mM, trained animals achieve higher rates of lactate removal for any given lactate concentration.

Animals↗

PubMed1982

Lactate and glucose exchange across the forearm, legs, and splanchnic bed during and after prolonged leg exercise.

The net exchange of glucose and lactate across the leg and the splanchnic bed and the arterialdeep venous (A-DV) differences for these substrates in the forearm were determined in healthy subjects during 3-3.5 h of leg exercise (bicycle ergometer) at 58% maximum O(2) uptake and during a 40-min post-exercise recovery period. Leg glucose uptake rose 16-fold during exercise and throughout the exercise period exceeded splanchnic glucose output. The latter reached a peak increment (3.5 times basal) at 90 min and fell by 60% during the third hour. As a result, blood glucose declined 40%, reaching frank hypoglycemia (blood glucose, <45 mg/dl) in 50% of subjects at 3.5 h. Splanchnic lactate uptake rose progressively during exercise to values four times the basal rate at 3 h in association with a rise in arterial lactate to 1.5 mM. There was, however, no significant net output of lactate from the legs beyond 90 min of exercise. In contrast, the A-DV lactate difference in the forearm became progressively more negative throughout exercise, reaching values three times the basal level at 3.5 h. The rise in arterial lactate during exercise was proportional to the elevation in plasma epinephrine, which rose ninefold. During recovery, splanchnic lactate uptake rose further to values six times the basal rate, whereas lactate output by the legs was no greater than in the basal state. The A-DV lactate difference in the forearm became even more negative than during exercise, reaching values four times basal. During exercise as well as recovery, forearm uptake of blood glucose could account for no more than 25-67% of forearm lactate release. Leg glucose uptake during recovery was threefold to fivefold higher than in the basal state in the face of plasma insulin concentrations that were 60% below basal and in association with a respiratory exchange ratio of 0.7. We conclude that (a) during prolonged leg exercise at 58% maximum O(2) uptake an imbalance between splanchnic glucose production and leg glucose utilization results in a fall in blood glucose that may reach hypoglycemic levels in healthy subjects; (b) there is a marked increase in the uptake of lactate by the splanchnic bed that cannot be attributed to increased output of lactate from the exercising legs; (c) lactate is released by forearm muscle and, together with other relatively inactive muscle, may be an important source of the increased lactate turnover during and after prolonged leg exercise; (d) the increasingly negative A-DV lactate difference in the forearm cannot be accounted for by uptake of blood glucose, suggesting the breakdown of glycogen in forearm muscle during and after leg exercise; (e) increased glucose uptake by the legs in association with hypoinsulinemia during recovery suggests an increase in insulin sensitivity that permits glycogen repletion in previously exercising muscle in the absence of food ingestion; and (f) the evidence for increased lactate output in the forearm and augmented glucose uptake in the legs during recovery raises the possibility that after leg exercise glycogen stores are decreasing in muscle that was relatively inactive (e.g., that of the forearm) while increasing in the previously exercising leg muscles.

Adult↗

PubMed1990

Late gestation alterations in fetal pulmonary lactate metabolism in vivo.

We have previously shown that lactate is produced by the ovine fetal lung. Inasmuch as factors that might affect lactate production, such as pulmonary glucose and oxygen uptake, change late in gestation we investigated whether pulmonary lactate metabolism also changes. Eleven chronically catheterized fetal lambs were studied over 119-141 d gestation. Lactate, glucose, and oxygen concentrations were measured in the pulmonary artery (PA) and vein while lung blood flow was determined using labeled microspheres. Between early studies (less than or equal to 127 d) and studies near term (greater than or equal to 134 d) PA lactate levels did not change, but due to increasing pulmonary blood flow, lung lactate delivery rose 51% (p less than 0.05). Because of a decline in PA glucose, lactate also made up a larger fraction of the major nonnitrogenous substrate in PA blood near term (p less than 0.001). Despite this, no net pulmonary uptake of lactate occurred. Lactate production continued, but decreased by 80% between early and late studies (p less than 0.05) and the maximum fraction of glucose uptake that could be accounted for by lactate production dropped from 0.78 to 0.20 (p less than 0.025). Correlations were found between lung lactate production and glucose uptake also correlated with PA glucose (p less than 0.05). No relationships were observed between lactate production and PA oxygen content, oxygen delivery, lactate concentration, or lactate delivery. The decreasing fraction of glucose uptake explained by lactate production suggests that metabolism of pulmonary glucose is altered near term. The correlation between decreasing glucose delivery and declining lactate production also suggests that glucose itself influences this change.

Animals↗

PubMed1991

Myocardial lactate metabolism during exercise.

The heart consumes lactate under resting conditions in normal healthy people. A limited number of studies have measured lactate exchange across the heart during exercise by using simultaneous arterial and coronary sinus catheterization. In general, exercise results in an increase in the rate of lactate uptake, which is due both to the increases in myocardial blood flow and lactate extraction from rest to exercise. Lactate extraction by the myocardium during submaximal exercise (40-60% VO2max) is largely dependent upon the concentration of lactate in arterial blood. Studies using a continuous infusion of 14C-lactate tracer have demonstrated that essentially all of the lactate taken up during exercise is immediately oxidized to CO2 in the myocardium. In addition, lactate tracer studies indicate that healthy myocardium simultaneously consumes and produces lactate under conditions of net lactate consumption. Moderate intensity exercise (40% VO2max) does not result in an increase in the rate of myocardial lactate production above resting values. Thus, the heart takes up lactate in proportion to the rate of lactate delivery to the myocardium both at rest and during exercise. Exercise that elicits an increase in the arterial lactate concentration above resting values results in an increase in the relative contribution of lactate oxidation to myocardial oxidative metabolism.

Coronary Vessels↗

PubMed1977

Metabolim of blood-borne lactate in rat brain in vivo.

L-Lactate uniformly labelled with 14C was administered to rats as a single intravenous injection. In experiments concerning the determination of lactate flux into total forebrain, the tissue was obtained by a freeze-clamping technique; in experiments concerning the determination of lactate flux in discrete brain areas the tissue was coagulated by microwave irradiation of the head. In the acid extract of brain tissue the contents and radioactivities of lactate, glucose and cycle amino acids were measured. The following results were obtained: 1. Labelled lactate in plasma equilibrates rapidly with lactate in a small pool in brain tissue. This accessible pool comprises one quarter of total brain lactate. Its size varies in brain regions being largest in cortex and smallest in pons and medulla. 2. Approximately one half of plasma-borne lactate in brain is used metabolically as is seen from the incorporation of lactate carbon in amino acids. The regional activity of lactate metabolism correlates with the local size of the accessible lactate pool. 3. The rates of lactate flux in total forebrain were approximated, the invasion of lactate from plasma to brain tissue to 0.4 mumol, the metabolisms of plasma-borne lactate to 0.2 mumol per g brain tissue min-1. 4. The labelling pattern of cycle amino acids is intermediate between the pattern from [14C]-glucose and [14c]-bicarbonate as precursors. This gives evidence for the influx of part of lactate into the "small" compartment of the citrate cycle along the CO2 fixation route with a predominant accumulation of lactate carbon in aspartate and glutamine.

Animals↗