Lactate uptake by the fetal sheep liver

Lactate is produced by the sheep placenta and is an important metabolic substrate for fetal sheep. However, lactate uptake and release by the fetal liver have not been assessed directly. We measured lactate flux across the liver in 16 fetal sheep at 129 (120-138) days gestation that had catheters chronically maintained in the fetal descending aorta, inferior vena cava, right or left hepatic vein, and umbilical vein. Lactate and hemoglobin concentrations and oxygen saturation were measured in blood drawn from all vessels. Umbilical venous, portal venous, and hepatic blood flow were measured by injecting radionuclide-labeled microspheres into the umbilical vein while obtaining a reference sample from the descending aorta. We found net hepatic uptake of lactate (5.0 +/- 4.4 mg/min per 100 g liver). A large quantity of lactate was delivered to the liver (94.2 +/- 78.1 mg/min per 100 g), so that the hepatic extraction of lactate was only 7.7 +/- 6.5%. Hepatic oxygen consumption was 3.18 +/- 3.3 ml/min per 100 g, and the hepatic lactate/oxygen quotient was 2.07 +/- 1.54. There was no significant correlation between hepatic lactate uptake and hepatic lactate or glucose delivery, hepatic oxygen consumption, hepatic blood flow, hepatic glucose flux, total body oxygen consumption, arterial pH, oxygen content, or oxygen saturation. There was, however, a significant correlation between hepatic lactate uptake and umbilical lactate uptake (r = 0.74, P less than 0.005) such that net hepatic lactate uptake was nearly equivalent to that produced across the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

High viable cell concentration fed-batch cultures of hybridoma cells through on-line nutrient feeding

A hybridoma cell line was cultivated in fed-batch cultures using a low-protein, serum-free medium. On-line oxygen uptake rate (OUR) measurement was used to adjust the nutrient feeding rate based on glucose consumption, which was estimated on-line using the stoichiometric relations between glucose and oxygen consumption. Through on-line control of the nutrient feeding rate, not only sufficients were supplied for cell growth and antibody production, but also the concentrations of glucose and other important nutrients such as amino acids were maintained at low levels during the cell growth phase. During the cultivation, cell metabolism changed from high lactate production and low oxygen consumption to low lactate production and high oxygen consumption. As a result the accumulation of lactate was reduced and the growth phase was extended. In comparison with the batch cultures, in which cells reached a concentration of approximately 2 x 10(6) cells/mL, a very high concentration of 1.36 x 10(7) cells/mL with a high cell viability (>90%) was achieved in the fed-batch culture. By considering the consumption of glucose and amino acids, as well as the production of cell mass, metabolites, and antibodies, a well-closed material balance was established. Our results demonstrate the value of coupling on-line OUR measurement and the stoichiometric realations for dynamic nutrient feeding in high cell concentration fed batch cultures. (c) 1995 John Wiley & Sons, Inc.     

Metabolic and hormonal responses in theophylline-increased cold resistance in males

The effects of theophylline (a phosphodiesterase inhibitor-adenosine receptor antagonist) and substrate feeding (Ensure, 250 kcal/235 ml) on cold resistance were studied in seminude males undertaking submaximal (50% maximum O2 consumption), intermittent (34% of total time) exercise in the cold (-5 to 15 degrees C, individually adjusted) for 3 h. Each subject (n = 7) served as his own control and was tested on a weekly schedule. Under control treatment, rectal temperature (Tre) decreased by 0.9 degrees C to approximately 36.2 degrees C after cold exposure, whereas under theophylline and Ensure, the decrease of Tre was only 0.4 degrees C, indicating a significant increase (P less than 0.05) in cold resistance (50% better than control). The plasma concentration of theophylline was 4.8-5.9 micrograms/ml and was positively correlated with plasma concentration of free fatty acids. Plasma norepinephrine (NE) increased significantly during cold exposure; the absolute concentration was significantly higher after theophylline pretreatment. The plasma concentrations of glucose, epinephrine, cortisol, and adenosine 3',5'-cyclic monophosphate did not change and the changes of free thyroxine and triiodothyronine were minor. Together, the effectiveness of theophylline + Ensure in acutely increasing cold resistance may be due to increased substrate availability for thermogenesis, part of which, through theophylline's potentiation of both sympathetic release of NE and NE-stimulated lipolysis and part of which, through supplementary feeding of Ensure.     

The transient responses of hybridoma cells to nutrient additions in continuous culture: II. Glutamine pulse and step changes

The transient and steady-state responses of hybridoma growth and metabolism to glutamine pulse and step changes have been examined. Metabolic quotients are reported for oxygen, glucose, lactate, ammonia, glutamine, alanine, and other amino acids. The specific glutamine consumption rate increased rapidly after all glutamine additions, but the responses of the glucose and oxygen consumption rates and the cell concentration were found to depend on the intial feed glutamine concentration. The glucose consumption rate was 1.4-10.9 times that of glutamine, and serine and branched-chain amino acids were consumed in larger amounts at the higher glucose: glutamine uptake ratios. It was estimated that maintenance accounted for ca. 60% of the cellular ATP requirements at specific growth rates ranging from 0.57 to 0.68 day(-1).     

Hindlimb glucose and lactate metabolism during umbilical cord compression and acute hypoxemia in the late-gestation ovine fetus

The metabolic adaptation of the hindlimb in the fetus to a reversible period of adverse intrauterine conditions and, subsequently, to a further episode of acute hypoxemia has been examined. Sixteen sheep fetuses were chronically instrumented with vascular catheters and transit-time flow probes. In nine of these fetuses, umbilical blood flow was reversibly reduced by 30% from baseline for 3 days (umbilical cord compression), while the remaining fetuses acted as sham-operated, age-matched controls. Acute hypoxemia was subsequently induced in all fetuses by reducing maternal fractional inspired oxygen concentration for 1 h. Paired hindlimb arteriovenous blood samples were taken at appropriate intervals during cord compression and acute hypoxemia, and by using femoral blood flow and the Fick principle, substrate delivery, uptake, and output were calculated. Umbilical cord compression reduced blood oxygen content and delivery to the hindlimb and increased hindlimb oxygen extraction and blood glucose and lactate concentration in the fetus. However, hindlimb glucose and oxygen consumption were unaltered during umbilical cord compression. In contrast, hindlimb oxygen delivery and uptake were significantly reduced in all fetuses during subsequent acute hypoxemia, but glucose extraction, oxygen extraction, and hindlimb lactate output significantly increased in sham-operated control fetuses only. Preexposure of the fetus to a temporary period of adverse intrauterine conditions alters the metabolic response of the fetal hindlimb to subsequent acute stress. Additional data suggest that circulating blood lactate may be derived from sources other than the fetal hindlimb under these circumstances. The lack of hindlimb lactate output during acute hypoxemia in umbilical cord-compressed fetuses, despite a significant fall in oxygen delivery to and uptake by the hindlimb, suggests that the fetal hindlimb may not respire anaerobically after exposure to adverse intrauterine conditions. hypoxia     

β-Karotinisomere in pflanzlichen Futterstoffen sowie ihre Veränderung durch Einflüsse der Werbung,Trocknung, Lagerung und Silierung

Crossbred wethers (22 months old; 46 ± 1.3 kg body weight), with catheters in a hepatic vein, the portal vein and a mesenteric vein and artery, consumed warm (W; bermudagrass hay) or cool season grass hay (C; ryegrass‐wheat) at 1.6% body weight (dry matter basis) in a crossover design experiment. Warm and cool season grasses were 13.6 and 9.9% crude protein, 77 and 66% neutral detergent fibre and 4.6 and 4.0% acid detergent lignin, respectively. Neutral detergent fibre digestibility (70.3 and 77.4%) and digestible energy intake (8.5 and 9.3 mJ/d) were greater (P<0.02) for C than for W, and digestible nitrogen intake (11.5 and 8.0 g/d for W and C, respectively) was greater (P<0.01) for W. Ruminai fluid concentrations of ammonia nitrogen and total volatile fatty acids were not altered by grass source, and acetate: propionate was greater (P<0.02) for W (3.80) than for the C (3.54). Portal‐drained viscera blood flow (118 and 119 1/h; SE 8.0), oxygen consumption (141 and 142 mM/h; SE 3.7), alpha‐amino nitrogen release (13.4 and 13.1 mM/h; SE 3.42), urea nitrogen uptake (22.8 and 22.5 mM/h; SE 4.97), ammonia nitrogen release (14.9 and 15.7 mM/h; SE 3.36), glucose uptake (10.0 and 6.5 mM/h; SE 1.30), propionate release (14.5 and 16.4 mM/h; SE 1.88), lactate release (4.64 and 5.03 mM/h; SE 1.908) and acetate release (54.8 and 55.4 mM/h for W and C, respectively; SE 8.82) were similar between grasses. Energy consumption by the portal‐drained viscera accounted for a slightly greater (P<0.01) percentage of digestible energy intake with W vs C (18.8 vs 17.0%; SE 0.10). In conclusion, with restricted consumption of W or C by mature sheep, grass source had little impact on net flux of oxygen and nutrients across the portal‐drained viscera and splanchnic bed.     

Cortisol induces perinatal hepatic gluconeogenesis in the lamb.

To examine the influence of a prenatal increase in plasma cortisol concentration on perinatal initiation of hepatic gluconeogenesis, we infused cortisol into seven fetal sheep at 137-140 days gestation. 14C-Lactate provided tracer substrate for estimation of gluconeogenesis. We measured hepatic blood flow using radionuclide-labeled microspheres. After delivery, fetal arterial blood glucose concentration (1.33 +/- 0.4 mmol/l) increased transiently, but returned to fetal levels within 1 h after delivery. Substantial hepatic gluconeogenesis was induced in the fetus after cortisol infusion, averaging 23.4 +/- 12.2 mumol/min/100 g liver (7.8 +/- 4.4 mumol/min/kg fetal weight). Fetal hepatic glucose output was 44.4 +/- 17.7 mumol/min/100 g liver. Hepatic glucose output did not change after delivery; estimated gluconeogenesis decreased immediately, then increased by 6 h after delivery. Lactate supply to the liver fell substantially, from 1.1 +/- 0.4 mmol/min/100 g in the fetus to 0.24 +/- 0.09 at 1 h after delivery. Lactate flux across the liver decreased from 75.3 +/- 23 mumol/min/100 g in the fetus to 20.2 +/- 15.7 at 1 h after delivery. Hepatic lactate flux was significantly related to gluconeogenesis (r = 0.734, P = 0.0001). We conclude that cortisol induces substantial hepatic gluconeogenesis in fetal sheep near term. After delivery, there appears to be a transient decline in gluconeogenesis from lactate, which may be secondary to limited hepatic oxygen and substrate supply. Onset of gluconeogenesis in the fetus fails to sustain increases in either fetal or postnatal blood glucose concentrations.     

Effect of restriction of placental growth on fetal and utero-placental metabolism

The effect of restriction of placental growth on the supply of glucose to the gravid uterus and fetus and on fetal and utero-placental metabolism of glucose and lactate was examined in this study. Endometrial caruncles were removed from 13 sheep (caruncle sheep) prior to mating, which restricted placental growth in the subsequent pregnancy. Half the fetuses of caruncle sheep were small or growth retarded, with the remainder normal in size. After insertion of vascular catheters at 110 days gestation, the caruncle sheep, together with 16 control sheep, were studied between 121 and 130 days of gestation. Glucose delivery to and consumption by the gravid uterus and its contents, both as a total and per kg of tissue mass, was significantly lower in caruncle ewes with small fetuses, although glucose extraction was similar to that in controls. Utero-placental glucose consumption was significantly lower in caruncle ewes carrying small fetuses compared to that in control ewes, both as a total and per kg of placenta. Small caruncle fetuses were hypoxaemic and hypoglycaemic and the lactate concentration in the common umbilical vein was significantly higher than in control sheep. Glucose delivery to and consumption by the fetus was significantly lower in normal-sized and in small caruncle fetuses compared to controls. Fetal glucose consumption per kg of fetus was similar in control and caruncle sheep. Fetal glucose extraction increased as fetal weight decreased. Utero-placental production of lactate was similar in control and caruncle ewes. However, uterine output of lactate decreased as placental weight fell. Utero-placental production of lactate per kg of placenta was significantly higher in caruncle ewes compared to controls and increased as oxygen content in blood from the fetal femoral artery decreased. Fetal lactate consumption per kg of fetus increased as the concentration of lactate in blood from the common umbilical vein increased. It is concluded that intrauterine growth retardation due to restriction of placental growth is associated with a reduced supply of glucose to both the pregnant uterus and fetus and a redistribution of glucose therein to the fetus, both directly as glucose and indirectly as lactate. This reflects the disproportionate maintenance of fetal weight relative to that of the placenta, reduced utero-placental consumption of glucose per kg of placenta, conversion of a greater proportion of that glucose or other substrate(s) to lactate by the placenta and an increase in the fraction of the lactate produced by utero-placental tissues that is secreted into the fetal circulation.     

Effects of dissolved oxygen on hybridoma cell growth, metabolism, and antibody production kinetics in continuous culture.

The effects of dissolved oxygen concentration (DO) on hybridoma cell physiology were examined in a continuous stirred tank bioreactor with a murine hybridoma cell line (167.4G5.3). Dissolved oxygen concentration was varied between 0% and 100% air saturation. Cell growth and viability, carbohydrate, amino acid, and energy metabolism, oxygen uptake, and antibody production rates were investigated. Cell growth was inhibited at both high and low DO. Cells could grow at 0% DO and maintain viability under a nitrogen atmosphere. Cell viability was higher at low DO. Glucose, glutamine, and oxygen consumption rates changed little at DO above 1% air saturation. However, the metabolic uptake rates changed below 1% DO, where growth became oxygen limited, and a Km value of 0.6% DO was obtained for the specific oxygen uptake rate. The metabolic rates of glucose, glutamine, lactate, and ammonia increased 2-3-fold as the DO dropped from 1% to 0%. Amino acid metabolism followed the same general pattern as that of glutamine and glucose. Alanine was the only amino acid produced. The consumption rates of amino acids changed little above 1% DO, but under anaerobic conditions the consumption rates of all amino acids increased severalfold. Cells obtained most of their metabolic energy from glutamine oxidation except under oxygen limitation, when glucose provided most of the energy. The calculated ATP production rate was only slightly influenced by DO and rose at 0% DO. Antibody concentration was highest at 35% DO, while the specific antibody production rate was insensitive to DO.     

Effect of lactate and beta-hydroxybutyrate infusions on brain metabolism in the fetal sheep

Brain uptake of substrates other than glucose has been demonstrated in neonatal but not fetal animals in vivo. This study was undertaken to investigate the ability of the fetal sheep brain to use potential alternative substrates when they were provided in increased amounts. Brain substrate uptake was measured in chronically catheterised fetal sheep during 2-h infusions of neutralised lactate (n = 12) or beta-hydroxybutyrate (n = 12). Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective infusions, no significant uptake of either substrate was demonstrated. However during both types of infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres (measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and the rise in lactate and butyrate concentrations during the butyrate infusions. Both substrates have metabolic actions that may inhibit brain glucose uptake. We speculate that the deleterious effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of brain glucose uptake.     

beta-Hydroxybutyrate is an alternative substrate for the fetal sheep brain.

Brain uptake of substrates other than glucose has been demonstrated in vivo in postnatal but not fetal life. In this study, brain uptake of potential alternative substrates beta-hydroxybutyrate and lactate was studied during 2 h substrate infusions in 10 chronically-catheterised fetal sheep at 135-141 days gestation. beta-hydroxybutyrate appeared to be taken up by the brain of 5 fetuses with spontaneously low arterial blood glucose concentrations, and produced by the brains of the 5 with higher glucose concentrations. Brain butyrate/oxygen quotients at the end of the infusions were directly related to fetal arterial blood glucose concentrations (r2 = 0.72, P less than 0.01. Brain butyrate/oxygen quotients were not related to the arterial beta-hydroxybutyrate concentrations at the beginning or end of the infusions. No brain uptake of lactate was demonstrated. This study suggests for the first time that the fetal brain in vivo may take up substrates other than glucose. The near term fetal sheep brain appears to take up beta-hydroxybutyrate only when arterial butyrate concentrations are high and glucose is low.     

Effect of meal and propranolol on whole body and splanchnic oxygen consumption in patients with cirrhosis

Our aim was to measure whole body energy expenditure after a mixed liquid meal, with and without simultaneous propranolol infusion, in patients with cirrhosis. We also wanted to investigate the effect of propranolol on substrate fluxes and oxygen uptake in the tissues drained by the hepatic vein and azygos vein in the postprandial period in these patients. Whole-body oxygen uptake, hepatic blood flow, hepatic venous pressure gradient and net-hepatic fluxes of oxygen, lactate, glucose, glycerol, and free fatty acids (FFA) were measured in 12 patients with alcoholic cirrhosis before and for 2 h after ingestion of a mixed liquid meal (700 kcal). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. The meal-induced energy expenditure was significantly lower in patients given propranolol [15.0 +/- 18.9 vs. 67.0 +/- 26.1 kJ/120 min (means +/- SD), P < 0.01]. Meal-induced whole body oxygen uptake was lower in patients receiving propranolol (19.2 +/- 38 vs. 135.7 +/- 61 mmol/120 min, P < 0.01), and the meal-induced increase in splanchnic oxygen uptake was nonexistent when propranolol was administered in combination (-13.2 +/- 34.8 vs. 110.4 +/- 34.8 mmol/120 min, P = 0.04). Postprandially, the propranolol group had a tendency toward a reduced splanchnic glucose output, and the FFA uptake was significantly reduced. Propranolol reduces meal-induced whole body oxygen uptake and energy expenditure as well as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole body oxygen consumption.     

Interrelationships and metabolic effects of fatty acids in the perfused rat liver at hyperthermic temperatures

Livers of fasted rats were perfused for 70 min at 37 degrees-43 degrees C in the presence or absence of acetate, octanoate or palmitate. Hepatic biosynthetic capacity was assessed by measuring rates of gluconeogenesis, ureogenesis, ketogenesis and O2 consumption. In the presence of each fatty acid, gluconeogenesis, ureogenesis and oxygen consumption were maintained at 37 degrees and 42 degrees C. At 43 degrees, the rate of glucose formation decreased markedly and rates of ureogenesis and oxygen consumption were distinctly lower. As the temperature was increased from 37 degrees to 43 degrees C without fatty acids, i.e. albumin only, there was a progressive decrease in the rate of gluconeogenesis while the ratio of net C3 utilized to glucose formed, increased successively. The values of this ratio in the presence of palmitate or octanoate at 43 degrees were smaller than those for albumin or acetate, but higher than the figure of 2 for complete conversion of C3 units to glucose. Although fatty acid was added in equimolar amounts of C2 units, total ketone formation was influenced significantly by chain length. Hepatic ketogenesis was similar at 37 degrees with albumin, palmitate, or acetate, but was stimulated significantly by octanoate at 37 degrees and 42 degrees C. At 42 degrees, ketone formation increased in the presence of palmitate. At 43 degrees C, ketogenesis with palmitate or octanoate decreased, while that with acetate or albumin was maintained at the same lower rates. The ratio of 3-hydroxybutyrate to acetoacetate in the perfusate was increased with palmitate at the end of perfusion at 37 degrees and 42 degrees C or octanoate at 42 degrees and 43 degrees C. Thus, long (palmitate)- and medium (octanoate)- but not short (acetate)-chain fatty acids enhance not only beta-oxidation, but influence the redox state of hepatic mitochondria with an increase in the state of reduction of the pyridine nucleotides. Such a shift in the redox state would be operable in the perfused liver even at 43 degrees C and may be responsible for improved conversion of lactate to glucose when medium- or long-chain fatty acids are present at hyperthermic temperatures.     

Nutrient and waste product concentration differences in upper and lower body arteries of fetal sheep

Well oxygenated blood returning from the placenta is preferentially shunted into the left side of the fetal heart and the ascending aorta. This results in higher oxygen saturation in arterial blood supplying the fetal upper body than in blood supplying the lower body. Since the placenta is also the site of nutrient and waste exchange, we evaluated differences in arterial concentrations of nutrients and waste products in fetal upper and lower body. Studies were carried out on ten, chronically catheterized, third trimester, fetal sheep. Blood samples, drawn simultaneously from the carotid and femoral arteries, were analyzed for glucose, oxygen saturation, oxygen content, total amino acids, lactate, urea nitrogen, and hydrogen ion concentration. Carotid arterial blood had higher levels of glucose (1.4 +/- 0.1 mg/dl (SEM); P less than 0.001), of alpha-amino nitrogen (0.4 +/- 0.1 mg/dl, equivalent to amino acid concentration difference of 2.5 mg/dl, P less than 0.025), of oxygen saturation (9.9 +/- 0.5%, P less than 0.001), and of oxygen content (1.0 +/- 0.1 ml/dl; P less than 0.001). Carotid values exceeded femoral by an average of 10% for glucose, 4% for amino nitrogen, 29% for oxygen saturation and 23% for oxygen content. Carotid arterial blood had lower urea nitrogen, (-0.5 +/- 0.2 mg/dl; P less than 0.05) and hydrogen ion (-1.1 +/- 0.1 nM/L; P less than 0.001) concentrations, but these differences averaged only 2% between vessels. Lactate concentration in the carotid and femoral arteries was the same. Fetal glucose and oxygen levels were closely related.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep

Epinephrine caused hyperglycemia in part by increasing gluconeogenesis. However, the mechanism of its gluconeogenic effects has not been studied in ruminants. This study was undertaken to examine the effect of epinephrine on the net hepatic uptake of selected glucose precursors in sheep. The major abdominal blood vessels of the sheep were catheterized in normal and alloxan diabetic sheep. Glucose production, metabolic clearance of glucose, and the hepatic removal of certain glucose precursors were determined before, during, and after epinephrine infusion. Epinephrine increased the hepatic glucose output, the concentrations of lactate and glycerol in plasma, and the net hepatic uptake and fractional hepatic extraction of lactate and glycerol. These effects were independent of changes in the concentrations of insulin and glucagon in plasma. These results show that epinephrine directly stimulates hepatic gluconeogenesis in sheep.     

Metabolic responses of the white shrimp, Penaeus vannamei, to ambient ammonia

Juvenile shrimp were individually exposed during 24 h to 0.007 (control), 0.36, 1.07, and 2.14 mmol/l total ammonia-N at 28 degrees C and 39 ppt salinity. After 22 h of ammonia-N exposure, oxygen consumption was measured for 2 h, and then hemolymph, hepatopancreas, and muscle tissues were sampled. Oxygen consumption, and levels of lactate and glycogen in the hepatopancreas increased significantly at the highest ammonia-N concentration. Concentration of oxyhemocyanin, acylglycerol, and cholesterol in hemolymph, and lactate in muscle decreased significantly in the group exposed to the highest ammonia levels. The changes observed in hemolymph and tissue metabolic fuels suggest a reduced use of carbohydrate through anaerobic metabolism and an increase in the use of lipids to satisfy the metabolic demand.     

Effects of exercise on mammary metabolism in the lactating ewe

Mammary metabolism in multiparous lactating ewes fed either lucerne chaff:barley grain (L:B; 70:30) or lucerne chaff:lupin grain (L:Lu; 70:30) diets was measured while at rest, during exercise on a treadmill at 0.7 m s⁻¹ on a 10 ° slope for 60 min, and during 30 min recovery from exercise. The effects of these treatments on plasma glucose, lactate, alpha-amino nitrogen (-amino N), non-esterified fatty acids (NEFA) and acetate were measured. Net mammary uptake of oxygen and metabolites was calculated from mammary blood flow and arteriovenous concentration (A − V) differences.

Mammary blood flow was reduced by 25% during exercise. Arterial concentrations of oxygen, glucose, lactate, -amino N and NEFA increased during exercise, whereas acetate concentration either remained unchanged or declined. Mammary A − V differences were significantly higher for oxygen, glucose, lactate and NEFA, and tended to be higher for -amino N and lower for acetate during exercise. The mammary uptakes of oxygen, glucose, lactate and -amino N were unaffected by exercise, whereas the uptake of NEFA was significantly increased and that of acetate was significantly reduced. The changes in arterial concentrations and mammary uptakes in response to exercise were not significantly affected by the diet. The responses in acetate and NEFA fluxes across the mammary gland might bring a change in the utilization of other metabolites as well as in the fatty acid composition of milk fat.     

Effect of insulin on gluconeogenesis and the metabolism of lactate in sheep

Owing to the fermentative nature of their digestion, ruminant animals are highly dependent upon gluconeogenesis to meet their glucose needs. The role of hormones in regulating this process is not clear. The purpose of this study was to examine the effect of insulin on the utilization of lactate in glucose synthesis in sheep. The euglycemic model was used in sheep. [U-14C]Lactate and [6-3H]glucose were infused to monitor lactate and glucose fluxes. Hepatic metabolism was measured using radioisotopic and venoarterial concentration difference techniques. Insulin concentrations increased from basal concentrations of 16 +/- 2 to 95 +/- 9 microU/mL. Insulin reduced the net hepatic utilization of lactate (303 +/- 43 vs. 120 +/- 27 mumol/min), hepatic extraction efficiency of lactate (29 +/- 4 vs. 9 +/- 2%), hepatic output of glucose (338 +/- 33 vs. 103 +/- 21 mumol/min), and incorporation of lactate into glucose (90 +/- 5 vs. 46 +/- 8 mumol/min). Insulin at physiological levels can inhibit hepatic gluconeogenesis in ruminants.     

Nitrogen Metabolism of the Human Brain

Cerebral nitrogen metabolism was studied in 29 healthy nonobese volunteers by means of a catheterization technique. Arterial levels and arterial-jugular venous (A-JV) concentration differences for amino acids, urea, ammonia, 5-oxoproline, glucose, and oxygen were measured in the basal, postabsorptive state and during an intravenous infusion of a commercial amino acid solution. In the basal state positive A-JV differences, indicating a net brain uptake, were noted for 12 of 22 amino acids as well as for ammonia. There was no significant net exchange for urea or for 5-oxoproline. During amino acid infusion, resulting in a 150-300% rise in arterial amino acid levels, the brain uptake of isoleucine, leucine, and tyrosine increased significantly, and a similar tendency was seen for most other amino acids. The infusion was accompanied by a 100% rise in arterial ammonia levels and a 10% increase in urea concentration. For ammonia the small positive A-JV difference in the basal state became markedly greater during amino acid infusion, whereas no significant alteration was noted for urea exchange across the brain. The A-JV differences for glucose and oxygen were positive in the basal state and unchanged during the infusion. The present findings demonstrate that in the basal state (a) there is a significant net brain uptake of most amino acids; (b) no single amino acid, urea, or 5-oxoproline is released from the brain; and (c) ammonia uptake occurs both in this state and during an amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic lactate uptake versus leg lactate output during exercise in humans.

The exponential rise in blood lactate with exercise intensity may be influenced by hepatic lactate uptake. We compared muscle-derived lactate to the hepatic elimination during 2 h prolonged cycling (62 +/- 4% of maximal O(2) uptake, (.)Vo(2max)) followed by incremental exercise in seven healthy men. Hepatic blood flow was assessed by indocyanine green dye elimination and leg blood flow by thermodilution. During prolonged exercise, the hepatic glucose output was lower than the leg glucose uptake (3.8 +/- 0.5 vs. 6.5 +/- 0.6 mmol/min; mean +/- SE) and at an arterial lactate of 2.0 +/- 0.2 mM, the leg lactate output of 3.0 +/- 1.8 mmol/min was about fourfold higher than the hepatic lactate uptake (0.7 +/- 0.3 mmol/min). During incremental exercise, the hepatic glucose output was about one-third of the leg glucose uptake (2.0 +/- 0.4 vs. 6.2 +/- 1.3 mmol/min) and the arterial lactate reached 6.0 +/- 1.1 mM because the leg lactate output of 8.9 +/- 2.7 mmol/min was markedly higher than the lactate taken up by the liver (1.1 +/- 0.6 mmol/min). Compared with prolonged exercise, the hepatic lactate uptake increased during incremental exercise, but the relative hepatic lactate uptake decreased to about one-tenth of the lactate released by the legs. This drop in relative hepatic lactate extraction may contribute to the increase in arterial lactate during intense exercise.