Biomedical subjects

Guillaume Py

Publications and source records attributed to Guillaume Py.

8 recordsLinked to original sources

PubMed2005

Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle.

To dissect the independent effects of altitude-induced hypoxemia and anorexia on the capacity for cardiac lactate metabolism, we examined the effects of 21 days of chronic hypobaric hypoxia (CHH) and its associated decrease in food intake and right ventricle (RV) hypertrophy on the monocarboxylate transporter 1 and 4 (MCT) expression, the rate of lactate uptake into sarcolemmal vesicles, and the activity of lactate dehydrogenase isoforms in rat muscles. In comparison with control rats (C), 1 mmol/L lactate transport measured on skeletal muscle sarcolemmal vesicles increased by 33% and 58% in hypoxic (CHH, barometric pressure = 495 hPa) and rats pair-fed an equivalent quantity of food to that consumed by hypoxic animals, respectively. The increased lactate transport was higher in PF than in CHH animals ( P < .05). No associated change in the expression of MCT1 protein was observed in skeletal muscles, whereas MCT1 mRNA decreased in CHH rats, in comparison with C animals (42%, P < .05), partly related to caloric restriction (30%, P < .05). MCT4 mRNA and protein increased during acclimatization to hypoxia only in slow-oxidative muscles (68%, 72%, P < .05, respectively). The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction. In both the left and right ventricles, the MCT1 protein content was unaffected by ambient hypoxia or restricted food consumption. These results suggest that MCT1 and MCT4 gene expression in fast-glycolytic muscles is mainly regulated by posttranscriptional mechanisms. Moreover, the results emphasize the role played by caloric restriction on the control of gene expression in response to chronic hypoxia and suggest that hypoxia-induced right ventricle hypertrophy failed to alter MCT proteins.

Animals↗

PubMed2005

Relationship between blood lactate concentration and substrate utilization during exercise in type 2 diabetic postmenopausal women.

Increased blood lactate concentration and alterations of substrate utilization have been shown to be partly involved in development of insulin resistance in obese and type 2 diabetic patients. As blood represents the first great distribution space and participates to lactate exchange in whole body, we investigated lactate transport in red blood cells at rest and the potential relationships between elevated blood lactate and substrate utilization in 7 obese controls and 7 obese type 2 diabetic postmenopausal women during an incremental exercise test. Blood samples were collected at rest, 30%, 50%, and 60% of maximal power and at 8 and 20 minutes of recovery time. Baseline lactatemia and its increase during exercise were higher in the diabetic group (P < .05). We found a negative correlation between basal and 30% maximal power lactatemia and 2 indexes of substrate utilization (crossover point: r = -0.79, r = -0.82 and maximal lipid oxidation point: r = -0.83, r = -0.80; P < .05) in diabetic group only. Furthermore, there were positive correlations between the affinity constant, maximal velocity transport, and basal lactate level in diabetic subjects (r = 0.91 and r = 0.73, respectively; P < .05). These results show that the elevation of blood lactate is associated with a greater carbohydrate oxidation in type 2 diabetes, but the mechanisms underlying the alteration of substrate utilization need to be clarified. Furthermore, increased lactate levels cannot be explained by alterations of lactate transport in red blood cells, but it could affect monocarboxylate transporter 1 properties.

Diabetes Mellitus, Type 2↗

PubMed2004

Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cyclo-ergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH (P < 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 +/- 87.8 vs. 1,035.9 +/- 114.8 nmol.ml(-1).min(-1); P < 0.05) and 41 mM (2,562.0 +/- 145.0 vs. 1,618.1 +/- 149.4 nmol.ml(-1).min(-1); P < 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM (P < 0.05) and 41 mM (P < 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM (r = -0.82, P < 0.05) and 41 mM (r = -0.84, P < 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity.

Adaptation, Physiological↗

PubMed2004

Opposite effects of in vitro lactate on erythrocyte deformability in athletes and untrained subjects.

Exercise transiently increases blood viscosity: however data on red cell deformability in this process remain inconsistent, since studies report either impairment (proportional to blood lactate accumulation), a lack of effect, or even in some cases an improvement. To test whether these inconsistencies may be due to physiological differences among populations studied, we compared the effects of in vitro lactate (2 mM, 4 mM and 10 mM) on erythrocyte rigidity in venous blood drawn at rest in 10 untrained vs 10 aerobically-trained subjects. After adjustment of osmolality and pH and incubation at 37 degrees C during 2 minutes, viscometric measurements were performed at 1000 s-1 with the MT90 (falling ball) viscometer and Dintenfass's 'Tk' was calculated. While at baseline there was no significant difference in Tk between the two groups, it decreased in the aerobically-trained subjects between 2 and 10 mM lactate concentrations (p<0.05) and increased in the untrained group between 2 and 4 mM (p<0.05). Thus, it seems that endurance training influences erythrocyte response to lactate. Lactate impaired erythrocyte deformability in untrained subjects but it (unexpectedly) improved it in trained subjects. This difference may be due to training-induced adaptations in erythrocyte metabolism, possibly including transmembrane transfer via monocarboxylate transporters.

Adaptation, Physiological↗

PubMed2003

The concept of maximal lactate steady state: a bridge between biochemistry, physiology and sport science.

The maximal lactate steady state (MLSS) is defined as the highest blood lactate concentration (MLSSc) and work load (MLSSw) that can be maintained over time without a continual blood lactate accumulation. A close relationship between endurance sport performance and MLSSw has been reported and the average velocity over a marathon is just below MLSSw. This work rate delineates the low- to high-intensity exercises at which carbohydrates contribute more than 50% of the total energy need and at which the fuel mix switches (crosses over) from predominantly fat to predominantly carbohydrate. The rate of metabolic adenosine triphosphate (ATP) turnover increases as a direct function of metabolic power output and the blood lactate at MLSS represents the highest point in the equilibrium between lactate appearance and disappearance both being equal to the lactate turnover. However, MLSSc has been reported to demonstrate a great variability between individuals (from 2-8 mmol/L) in capillary blood and not to be related to MLSSw. The fate of enhanced lactate clearance in trained individuals has been attributed primarily to oxidation in active muscle and gluconeogenesis in liver. The transport of lactate into and out of the cells is facilitated by monocarboxylate transporters (MCTs) which are transmembrane proteins and which are significantly improved by training. Endurance training increases the expression of MCT1 with intervariable effects on MCT4. The relationship between the concentration of the two MCTs and the performance parameters (i.e. the maximal distance run in 20 minutes) in elite athletes has not yet been reported. However, lactate exchange and removal indirectly estimated with velocity constants of the individual blood lactate recovery has been reported to be related to time to exhaustion at maximal oxygen uptake.

Adaptation, Physiological↗

PubMed2002

Effects of prolonged mechanical ventilation on respiratory muscle ultrastructure and mitochondrial respiration in rabbits.

OBJECTIVE: To investigate in rabbits whether prolonged mechanical ventilation (PMV) leads to ultrastructural changes in respiratory muscles and alters diaphragm mitochondrial respiration. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: We studied respiratory muscles of seven rabbits after 49+/-1 h of controlled mechanical ventilation. Ten nonventilated rabbits were used as a control group. MEASUREMENTS AND RESULTS: After mechanical ventilation electron-microscopic observations of the diaphragm and the external intercostal muscles revealed disrupted myofibrils, increased number of lipid vacuoles in the sarcoplasm, and smaller mitochondria with focal membrane disruptions. Volumetric and numerical densities of the mitochondria were significantly lower in the PMV group than the control group. Mitochondrial respiration was quantified in isolated diaphragm muscle-cell mitochondria using two respiratory substrates. There was no difference in oxygen consumption values in the three states of mitochondrial respiration between the two groups except for state 2 (basal state) with pyruvate/malate parameter (53.5+/-20 for the ventilated group vs. 33.8+/-10.2 nmol atom O/mg per minute for the control group). There was no significant difference between groups in ADP/O ratio or respiratory control ratio. CONCLUSIONS: PMV leads to respiratory muscle cell degeneration and minor changes in oxidative phosphorylation coupling in diaphragmatic mitochondria. These phenomena may mediate part of damage of respiratory muscles after inactivity related to PMV.

Animals↗

PubMed2002

Effects of streptozotocin-induced diabetes on markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters.

Diabetes is known to alter both oxidative and glycolytic pathways in a fiber type-dependent manner. In various skeletal muscles of normal rats, monocarboxylate transporter 1 (MCT1) has been found to be highly correlated to lactate uptake, as well as to oxidative capacity, whereas the distribution and characteristics of MCT4 make it a good candidate for the extrusion of lactic acid from glycolytic muscle cells. Since a previous study found decreased sarcolemmal lactate uptake in streptozotocin (STZ)-diabetic rats, we investigated the presence of MCT1 in relation to enzymatic markers of both oxidative and glycolytic pathways, as well as MCT4 content, in STZ-diabetic rats. Soleus (SOL), red tibialis anterior (RTA), extensor digitorus longus (EDL), heart, and preparations of purified sarcolemmal vesicles (SV) from control and STZ-diabetic rats were harvested for MCT1 and MCT4 content, citrate synthase activity (CS), and lactate dehydrogenase (LDH) isozymes. Basal blood lactate concentration was increased by 38% in the diabetic rats (close to 1.91 mmol/L). However, no change was found in either MCT1 or MCT4 content in these rats. The diabetic rats presented fiber type-specific decrease in CS activity. We noted a redistribution in LDH isozymes in diabetic muscles with a general increase in type H-LDH. Regression analyses indicated (1) a strong relationship between LDH-4 and LDH-5 and (2) MCT1 was still correlated with CS activity in diabetic muscles. These results suggest that diabetes-induced hyperlactatemia is not associated with changes in MCT1 or MCT4 expression, but with alterations of oxidative and glycolytic enzymes.

Animals↗

PubMed2002

Effect of prolonged undernutrition on rat diaphragm mitochondrial respiration.

Previous studies have shown that undernutrition induces an impairment of the respiratory muscle function in patients with chronic lung disease. To explain this, we hypothesized that undernutrition could decrease oxidative metabolism in the diaphragm. We therefore examined the effect of prolonged undernutrition on diaphragm mitochondrial oxygen uptake with pyruvate and palmitate as substrates in adult rats. Ten rats served as controls (CTL). Ten nutritionally deprived rats (ND) received 40% of their estimated daily nutrition. Five weeks of undernutrition induced a 33% decrease in state 3 respiration with pyruvate plus malate as substrate (993 +/- 171 versus 1488 +/- 167 nmol atomic O/mg/min, P < 0.01) and a 39% decrease with palmitate plus malate (516 +/- 89 versus 850 +/- 165 nmol atomic O/mg/min, P < 0.05). With succinate plus rotenone, there was no significant difference in the respiratory rate between groups. In the ND group, we found a significant decrease in citrate synthase activity (P < 0.01), and also in reduced nicotinamine adenine dinucleotide (NADH) dehydrogenase activity (P < 0.05), which cannot alone induce such a state 3 respiratory decrease. This showed that undernutrition in rat diaphragm does not induce an alteration in protein complexes I, II, III, and IV, or the F complex containing the mitochondrial ATPase of the electron transport chain. In conclusion, the main result of this study was that prolonged undernutrition induced a decrease in mitochondrial respiration secondary to a significant reduction in NADH generation by the Krebs cycle, which may affect respiratory muscle function with implications for patient care.

Animal Nutritional Physiological Phenomena↗