Delayed labelling of brain glutamate after an intra-arterial [13C]glucose bolus: evidence for aerobic metabolism of guinea pig brain glycogen store.
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Glycogen in glial cells is the largest store of glucose equivalents in the brain. Here we describe evidence that brain glycogen contributes to aerobic energy metabolism of the guinea pig brain in vivo. Five min after an intra-arterial bolus injection of d-[U-14C]glucose, 28+/-11% of the radioactivity in brain tissue was associated with the glycogen fraction, indicating that a significant proportion of labelled glucose taken up by the brain is converted to glycogen shortly after bolus infusion. Incorporation of 13C-label into lactate generated by brains made ischaemic after d-[1-13C]glucose injection confirms that these glucose equivalents can be mobilised for anaerobic glucose metabolism. Aerobic metabolism was monitored by following the time course of 13C-incorporation into glutamate in guinea pig cortex and cerebellum in vivo. After an intra-arterial bolus injection of d-[1-13C]glucose, glutamate labelling reached a maximum 40-60 min after injection, suggesting that a slowly metabolised pool of labelled glucose equivalents was present. As the concentration of 13C-labelled glucose in blood was shown to decrease below detectable levels within 5 min of bolus injection, this late phase of glutamate labelling must occur with mobilisation of a brain storage pool of labelled glucose equivalents. We interpret this as evidence that glucose equivalents in glycogen may contribute to energy metabolism in the aerobic guinea pig brain. (+info)
Bicarbonate/lactate dialysis solution improves in vivo function of peritoneal host defense in rats.
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OBJECTIVE: To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonate-lactate-buffered dialysis fluid. METHODS: Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/L lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 g/dL (Lac); and, (2) 15 mmol/L lactate and 25 mmol/L bicarbonate-buffered fluid, pH 7.0-7.5, with a glucose concentration of 2.27 g/dL (Bic-Lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (LPS)] to induce peritonitis. RESULTS: During PET 1 no consistent differences were detected in peritoneal permeability between the Lac and Bic-Lac groups. Total dialysate cell count in the Bic-Lac animals was lower than in rats treated with Lac fluid: that is, at 8 hours, the respective counts were 1858+/-524 cells/microL versus 2785+/-1162 cells/microL (p < 0.01). Dialysate from animals dialyzed with Bic-Lac contained more macrophages (at 4 hours: 53.6%+/-35.8% versus 35.8%+/-8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6%+/-1.8% versus 15.4%+/-6.1%, p < 0.001) as compared to those dialyzed with the Lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-Lac rats was lower than that in the Lac group (0.98+/-0.28 micromol/mL versus 2.32+/-0.87 micromol/mL, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the increase in peritoneal permeability resulting from the LPS-induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the Lac group versus the Bic-Lac group (at 8 hours: 8789+/-4862 cells/microL versus 3961+/-581 cells/microL, p < 0.001), contained more neutrophils (at 8 hours: 80.0%+/-11.3% versus 54.8%+/-4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8%+/-5.6% versus 21.2%+/-3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFalpha: +53%, p < 0.05) and of interferon gamma (IFN-gamma: +303%, p < 0.02), in the Bic-Lac group than in the Lac group. CONCLUSIONS: A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-Lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-Lac solution possess an augmented ability to produce inflammatory cytokines. (+info)
Stimulation of both aerobic glycolysis and Na(+)-K(+)-ATPase activity in skeletal muscle by epinephrine or amylin.
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Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in skeletal muscle. However, it is not known whether these hormones stimulate glycolytic ATP production that is specifically coupled to ATP consumption by the Na(+)-K(+) pump. These studies correlated glycolysis with Na(+)-K(+)-ATPase activity in resting rat extensor digitorum longus and soleus muscles incubated at 30 degrees C in well-oxygenated medium. Lactate production rose three- to fourfold, and the intracellular Na(+)-to-K(+) ratio (Na(+)/K(+)) fell with increasing concentrations of epinephrine or amylin. In muscles exposed to epinephrine at high concentrations (5 x 10(-7) and 5 x 10(-6) M), ouabain significantly inhibited glycolysis by approximately 70% in either muscle and inhibited glycogenolysis by approximately 40 and approximately 75% in extensor digitorum longus and soleus, respectively. In the absence of ouabain, but not in its presence, statistically significant inverse correlations were observed between lactate production and intracellular Na(+)/K(+) for each hormone. Epinephrine had no significant effect on oxygen consumption or ATP content in either muscle. These results suggest for the first time that stimulation of glycolysis and glycogenolysis in resting skeletal muscle by epinephrine or amylin is closely linked to stimulation of active Na(+)-K(+) transport. (+info)
Effects of FI(O(2)) on hemodynamic responses and O(2) transport during RSR13-induced reduction in P(50).
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Reduced Hb-O(2) affinity facilitates O(2) release to tissue but may impair pulmonary O(2) uptake, affecting cardiac output and systemic vascular resistance (SVR). We studied the effects of shifting the O(2)-dissociation curve (ODC) to the right with a continuous infusion of RSR13, an allosteric modifier of Hb, and of different inspired O(2) fractions (FI(O(2))) on arterial O(2) saturations (Sa(O(2))) in Hb and on hemodynamics in nonanesthetized rats. At an FI(O(2)) of 0.21, Sa(O(2)) fell during RSR13 from 95 to 81%. Elevation of FI(O(2)) to 0.30 returned Sa(O(2)) to baseline in the RSR13 group. The decrease in mean arterial pressure (MAP) was significantly greater in the control than in the RSR13 group at 30% O(2). Cardiac index (CI) increased only during RSR13 at 21% O(2) and returned to baseline at 30% O(2). In contrast, SVR decreased after RSR13 was infused at 21% O(2) but returned to baseline at 30%O(2), whereas controls showed the opposite, a sustained SVR. In the follow-up period, when 21 O(2)% was reestablished and mild anemia was present, MAP and SVR fell significantly more in controls, whereas CI only increased in controls. Lactate was significantly lower in the RSR13 than in the control group during RSR13 and the follow-up period. These results demonstrate that 1) continuous infusion of RSR13 produces a constant shift in the O(2) tension at which Hb is 50% saturated (P(50)), 2) FI(O(2)) of 0.30 compensates for the effects of increased P(50) on pulmonary O(2) loading, and 3) right-shifted ODC combined with supplemental O(2) may improve tissue O(2) availability. (+info)
Hormonal and metabolic responses to maintained hyperglycemia during prolonged exercise.
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We studied the effects of maintained hyperglycemia (12 mmol/l) on endurance exercise to determine the hormonal and metabolic responses, the maximal rate of glucose infusion (i.e., utilization), and the effects on muscle glycogen stores. Eight men undertook two trials during which they exercised on a cycle ergometer at an intensity of approximately 70% peak O(2) uptake for 120 min. In the first trial (trial A), subjects had their blood glucose concentration clamped at 12 mmol/l 30 min before exercise and throughout exercise. The same rate and volume of infusion of saline as had occurred for trial A were used in a placebo trial (trial B). Maintained hyperglycemia resulted in significantly lowered plasma concentrations of nonesterified fatty acid, glycerol, 3-hydroxybutyrate, epinephrine, norepinephrine, and growth hormone (P < 0.001) during exercise, whereas concentrations of plasma insulin were significantly elevated (P < 0.001). Calculations of the rates of total carbohydrate oxidation showed that trial A resulted in significantly higher values when compared with trial B (P < 0.01) and that the maximal rates of glucose infusion varied between 1.33 and 2.78 g/min at 100-120 min. Muscle glycogen concentrations were significantly depleted (P < 0.01) after both trials (trial A, 170.3 micromol/g dry wt decrease; trial B, 206 micromol/g dry wt decrease), although this apparent difference may be accounted for by storage of 22.6 g glucose during the 30-min prime infusion. The results from this study confirm that maintained hyperglycemia attenuates the hormonal response and promotes carbohydrate oxidation and utilization and that muscle glycogen may not be spared. (+info)
Training-induced elevation in FABP(PM) is associated with increased palmitate use in contracting muscle.
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To evaluate the effects of endurance training in rats on fatty acid metabolism, we measured the uptake and oxidation of palmitate in isolated rat hindquarters as well as the content of fatty acid-binding proteins in the plasma membranes (FABP(PM)) of red and white muscles from 16 trained (T) and 18 untrained (UT) rats. Hindquarters were perfused with 6 mM glucose, 1,800 microM palmitate, and [1-(14)C]palmitate at rest and during electrical stimulation (ES) for 25 min. FABP(PM) content was 43-226% higher in red than in white muscles and was increased by 55% in red muscles after training. A positive correlation was found to exist between succinate dehydrogenase activity and FABP(PM) content in muscle. Palmitate uptake increased by 64-73% from rest to ES in both T and UT and was 48-57% higher in T than UT both at rest (39.8 +/- 3.5 vs. 26.9 +/- 4. 4 nmol. min(-1). g(-1), T and UT, respectively) and during ES (69.0 +/- 6.1 vs. 43.9 +/- 4.4 nmol. min(-1). g(-1), T and UT, respectively). While the rats were resting, palmitate oxidation was not affected by training; palmitate oxidation during ES was higher in T than UT rats (14.8 +/- 1.3 vs. 9.3 +/- 1.9 nmol. min(-1). g(-1), T and UT, respectively). In conclusion, endurance training increases 1) plasma free fatty acid (FFA) uptake in resting and contracting perfused muscle, 2) plasma FFA oxidation in contracting perfused muscle, and 3) FABP(PM) content in red muscles. These results suggest that an increased number of these putative plasma membrane fatty acid transporters may be available in the trained muscle and may be implicated in the regulation of plasma FFA metabolism in skeletal muscle. (+info)
Blood lactate accumulation and muscle deoxygenation during incremental exercise.
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Near-infrared spectroscopy (NIRS) could allow insights into controversial issues related to blood lactate concentration ([La](b)) increases at submaximal workloads (). We combined, on five well-trained subjects [mountain climbers; peak O(2) consumption (VO(2peak)), 51.0 +/- 4.2 (SD) ml. kg(-1). min(-1)] performing incremental exercise on a cycle ergometer (30 W added every 4 min up to voluntary exhaustion), measurements of pulmonary gas exchange and earlobe [La](b) with determinations of concentration changes of oxygenated Hb (Delta[O(2)Hb]) and deoxygenated Hb (Delta[HHb]) in the vastus lateralis muscle, by continuous-wave NIRS. A "point of inflection" of [La](b) vs. was arbitrarily identified at the lowest [La](b) value which was >0.5 mM lower than that obtained at the following. Total Hb volume (Delta[O(2)Hb + HHb]) in the muscle region of interest increased as a function of up to 60-65% of VO(2 peak), after which it remained unchanged. The oxygenation index (Delta[O(2)Hb - HHb]) showed an accelerated decrease from 60- 65% of VO(2 peak). In the presence of a constant total Hb volume, the observed Delta[O(2)Hb - HHb] decrease indicates muscle deoxygenation (i.e., mainly capillary-venular Hb desaturation). The onset of muscle deoxygenation was significantly correlated (r(2) = 0.95; P < 0.01) with the point of inflection of [La](b) vs., i.e., with the onset of blood lactate accumulation. Previous studies showed relatively constant femoral venous PO(2) levels at higher than approximately 60% of maximal O(2) consumption. Thus muscle deoxygenation observed in the present study from 60-65% of VO(2 peak) could be attributed to capillary-venular Hb desaturation in the presence of relatively constant capillary-venular PO(2) levels, as a consequence of a rightward shift of the O(2)Hb dissociation curve determined by the onset of lactic acidosis. (+info)
Validity of the heart rate deflection point as a predictor of lactate threshold during running.
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During an incremental run test, some researchers consistently observe a heart rate (HR) deflection at higher speeds, but others do not. The present study was designed to investigate whether differences in test protocols could explain the discrepancy. Additionally, we sought to determine whether the HR deflection point accurately predicts lactate threshold (LT). Eight trained runners performed four tests each: 1) a treadmill test for maximal O(2) uptake, 2) a Conconi test on a 400-m track with speeds increasing approximately 0.5 km/h every 200 m, 3) a continuous treadmill run with speeds increasing 0.5 km/h every minute, and 4) a continuous LT treadmill test in which 3-min stages were used. All subjects demonstrated an HR deflection on the track, but only one-half of the subjects showed an HR deflection on the treadmill. On the track the shortening of stages with increasing speeds contributed to a loss of linearity in the speed-HR relationship. Additionally, the HR deflection point overestimated the LT when a continuous treadmill LT protocol was used. In conclusion, the HR deflection point was not an accurate predictor of LT in the present study. (+info)