Biomedical subjects

Jacques Mercier

Publications and source records attributed to Jacques Mercier.

At least 19 recordsLinked to original sources

PubMed2007

Pyruvate modifies glycolytic and oxidative metabolism of rat embryonic spinal cord astrocyte cell lines and prevents their spontaneous transformation.

This study aimed to provide detailed data on mitochondrial respiration of normal astrocyte cell lines derived from rat embryonic spinal cord. Astrocytes in early passages (EP), cultured without pyruvate for more than 35 passages, defined here as late passages (LP), undergo spontaneous transformation. To study initial steps in cell transformation, EP data were compared with those of LP cells. LP cells had reduced glycolysis, fewer mitochondria and extremely low oxidative rates, resulting from a dysfunction of complexes I and II + III of the respiratory chain. Treatment of EP cells with pyruvate until they were, by definition, LP cultures prevented transformation of these cells. Pyruvate-treated EP cells had more mitochondria than normal cells but slightly lower respiratory rates. The increase of mitochondrial content thus appears to act as a compensatory effect to maintain oxidative phosphorylation in these LP 'non-transformed' cells, in which mitochondrial function is reduced. However, pyruvate treatment of transformed LP cells during additional passages did not significantly restore their oxidative metabolism. These data highlight changes accompanying spontaneous astrocyte transformation and suggest potential targets for the control of astrocyte proliferation and reaction to various insults to the central nervous system.

Aging↗

PubMed2006

Differential localization of autolyzed calpains 1 and 2 in slow and fast skeletal muscles in the early phase of atrophy.

Calpains have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. However, limited data are available about the specific involvement of each calpain in the early stages of muscle atrophy. The aims of this study were to determine whether calpains 1 and 2 are autolyzed after a short period of muscle disuse, and, if so, where in the myofibers the autolyzed products are localized. In the rat soleus muscle, 5 days of immobilization increased autolyzed calpain 1 in the particulate and not the soluble fraction. Conversely, autolyzed calpain 2 was not found in the particulate fraction, whereas it was increased in the soluble fraction after immobilization. In the less atrophied plantaris muscle, no difference was noted between the control and immobilized groups whatever the fraction or calpain. Other proteolytic pathways were also investigated. The ubiquitin-proteasome pathway was activated in both skeletal muscles, and caspase 3 was activated only in the soleus muscle. Taken together, our data suggest that calpains 1 and 2 are involved in atrophy development in slow type muscle exclusively and that they have different regulation and protein targets. Moreover, the activation of proteolytic pathways appears to differ in slow and fast muscles, and the proteolytic mechanisms involved in fast-type muscle atrophy remain unclear.

Animals↗

PubMed2006

High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle.

The regulation of intracellular pH during intense muscle contractions occurs via a number of different transport systems [e.g., monocarboxylate transporters (MCTs)] and via intracellular buffering (beta m(in vitro)). The aim of this study was to investigate the effects of an acute bout of high-intensity exercise on both MCT relative abundance and beta m(in vitro) in humans. Six active women volunteered for this study. Biopsies of the vastus lateralis were obtained at rest and immediately after 45 s of exercise at 200% of maximum O2 uptake. Beta m(in vitro) was determined by titration, and MCT relative abundance was determined in membrane preparations by Western blots. High-intensity exercise was associated with a significant decrease in both MCT1 (-24%) and MCT4 (-26%) and a decrease in beta m(in vitro) (-11%; 135 +/- 3 to 120 +/- 2 micromol H+ x g dry muscle(-1) x pH(-1); P < 0.05). These changes were consistently observed in all subjects, and there was a significant correlation between changes in MCT1 and MCT4 relative abundance (R2 = 0.92; P < 0.05). In conclusion, a single bout of high-intensity exercise decreased both MCT relative abundance in membrane preparations and beta m(in vitro). Until the time course of these changes has been established, researchers should consider the possibility that observed training-induced changes in MCT and beta m(in vitro) may be influenced by the acute effects of the last exercise bout, if the biopsy is taken soon after the completion of the training program. The implications that these findings have for lactate (and H+) transport following acute, exhaustive exercise warrant further investigation.

Adolescent↗

PubMed2006

Effects of intermittent hypoxic training on amino and fatty acid oxidative combustion in human permeabilized muscle fibers.

The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions ( approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2 ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08 mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max), and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2006

Evaluation of insulin sensitivity and glucose effectiveness during a standardized breakfast test: comparison with the minimal model analysis of an intravenous glucose tolerance test.

There is a need for reliable measurements of insulin sensitivity (SI) simpler than the euglycemic hyperinsulinemic clamp or the intravenous glucose tolerance test (IVGTT), which could be used when the simpler surrogates based on fasting insulin (Ib) and glucose (Gb) lose their validity. Several evaluations of SI derived from oral glucose tolerance test (OGTT) or its physiologic form, the standardized breakfast test (SBT), have been proposed. We aimed at determining which SBT-derived measurements of SI give the best prediction of the values obtained with the minimal model analysis of an IVGTT. Twenty-eight subjects (23 females and 5 males; age, 44.3+/-0.6 years) with a wide range of glucose tolerance randomly underwent a hyperglucidic SBT and an IVGTT with minimal model analysis. Correlations of 35 indices (converted if appropriated into similar units) with IVGTT-derived SI were calculated, and the accuracy of the empiric formulas obtained with the 11 best predictions were evaluated with Bland-Altman plots. Subjects covered all the spectrum of SI between 0.19 and 21.3 min-1/(microU.mL-1)x10(-4). Eight procedures yielded satisfactory predictions of minimal model SI: (1) SI (from Matsuda's composite index)=-1.24+65/(IbGbImGm)-0.5; (2) SI=1.89+2690/(IbGbImGm); (3) SI (from Bennett's index)=-2.93+5.16/(log Ibxlog Gb); (4) SI (from Sluiter's index)=0.2+2400/(IpGp); (5) SI=-8.54+38.4/(Belfiore's ISI index); (6) SI (from Cederholm's formula)=76/(Gm log Im); (7) SI=0.248+0.947/GbIm; (8) SI (from Mari's "oral glucose insulin sensitivity" index)=oral glucose insulin sensitivity/Ip; (9) Caumo's model. Glucose effectiveness Sg can also be accurately predicted by the following formula: Sg=2.921e-0.185(G60- Gb) (Ip=insulin peak; Gp=glucose peak; Ia=insulin area; Ga=glucose area; G60=glycemia at 60 minutes). The hyperglucidic SBT can provide accurate evaluations of SI and Sg, either by elaborated models or by simple empiric formulas.

Adolescent↗

PubMed2006

The hemorheological aspects of the metabolic syndrome are a combination of separate effects of insulin resistance, hyperinsulinemia and adiposity.

The metabolic syndrome which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated, contributing to a various extent to a global impairment of blood rheology. We previously reported in 157 nondiabetic subjects that both obesity and insulin resistance increase red cell rigidity (Dintenfass's Tk) and plasma viscosity (eta p), and that whole blood viscosity at high shear rate (eta b 1000 s(-1)) reflects rather obesity than insulin resistance. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 81 subjects into 4 subgroups according to quartiles of insulin sensitivity (SI) (measured with the minimal model of an intravenous glucose tolerance test) and baseline insulin. Results show that (1) values of SI within the upper quartile are associated with low eta b due to low eta p; (2) low SI regardless insulinemia is associated with increased aggregation indexes; (3) when low SI is associated with hyperinsulinemia (insulin the upper quartile and SI in the lower) there is a further increase in eta b due to an increase in eta p; (4) neither SI nor insulinemia modify Hct. Thus hyperinsulinemia and insulin resistance induce hyperviscosity syndromes which are somewhat different, although they are associated most of the time. Low SI increases RBC aggregation while hyperinsulinemia increases eta p.

Adiposity↗

PubMed2006

Hemorheological disturbances correlate with the lipid profile but not with the NCEP-ATPIII score of the metabolic syndrome.

The metabolic syndrome, which is associated with an high risk for diabetes and atherothrombosis, is associated with hemorheologic abnormalities. These abnormalities seem more and more to be explained by its various symptoms than by insulin resistance which represents theoretically the core of the syndrome. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 90 subjects into 4 subgroups according to the clinical score "NCEP-ATPIII" which is the best recognized standardized definition of the syndrome. Results show no significant changes of blood rheology across classes of NCEP score despite a borderline rank correlation between RBC aggregability "M1" and the score. Whole blood viscosity was mostly correlated to HDL-cholesterol (r = -0.353, p = 0.007) and triglycerides (r = 0.574, p = 0.0001). Plasma viscosity was correlated with total cholesterol (r = 0.3359, p = 0.02) and with LDL-cholesterol (r = 0.357, p = 0.03). Red blood cell rigidity "Tk" was negatively correlated to HDL-cholesterol (r = -0.430, p = 0.007). Aggregability "M" was correlated to total cholesterol (r = 0.356, p = 0.01) and "M1" to HDL-cholesterol (r = -0.406, p = 0.006). Thus, despite previously described correlations with glucose disposal parameters, the hyperviscosity syndrome of the metabolic syndrome is not proportional to its clinical scoring and is strongly dependent upon the lipid profile.

Blood Viscosity↗

PubMed2006

Partially opposite hemorheological effects of aging and training at middle age.

Aging impairs blood rheology while various training protocols improve it. The purpose of this study was to delineate the respective role of aging and endurance training on blood rheology. Thirty-two subjects [16 middle-aged men: 8 cyclists (MAcy) and 8 sedentary men (MAsed) and 16 young men: 8 cyclists (Ycy) and 8 sedentary men (Ysed)] were compared in this study. Results showed higher red blood cell (RBC) rigidity and aggregability (AFFIBIO), lower RBC disaggregability (AFFIBIO) at middle age than at 25 yr, regardless of training status. However there was no age-related difference in whole blood viscosity at either native or corrected hematocrit, plasma viscosity, hematocrit, and Myrenne aggregation indexes M and M1. Training was associated with a reduced hematocrit in middle age subjects but not in 25 yr old ones. We evidenced no effect of training on red cell rigidity (Dintenfass's Tk index), in whole blood viscosity at either native or corrected hematocrit, and plasma viscosity. Thus, regular cycling at middle age maintains a low hematocrit but does not prevent aging-related increase in red cell rigidity and aggregability. Specific effects of cycling among other sports may explain this specific pattern.

Adult↗

PubMed2006

Is plasma viscosity a predictor of overtraining in athletes?

There is a lack of consensus about the biological diagnosis of the overtraining syndrome (OTS). Recently, efforts have been made to standardize its clinical diagnosis (e.g., standardized questionnaires like that of the French consensus group on overtraining of the Société Française de Médecine du Sport-SFMS). We previously reported that the early signs of overtraining (= "overreaching") in elite sportsmen are associated with a hemorheologic pattern (raised hematocrit and plasma viscosity etap) that suggests some degree of reversal of the "autohemodilution" which characterizes fitness, and that the feeling of heavy legs in overtrained athletes is related to higher etap and higher red cell aggregation. We thus investigated on a sample of 48 athletes (age 24 +/- 1 yr), referred for possible diagnosis of overtraining to what extent plasma viscosity is a predictor of OTS. From those 48 athletes 10 had a value of etap in the highest quartile (etap > 1.44 pPa.s) and 8 of them had a diagnosis of overreaching, while in the 38 whose etap was < 1.44 mPa.s there were 20 cases of overreachings. Overt cases of OTS were found in 1 subject of the highest quintile and two in the lowest. Thus the predictive value of etap for early stages (overreaching) or chronicized stages (overtraining syndrome) is as follows: (a) prediction of overreaching: sensitivity 28.57%; specificity 90%; positive predictive value 80%; negative predictive value 47.37%; (b) prediction of chronicized overtraining: sensitivity 2.70%; specificity 18.18%; positive predictive value; 10.00%; negative predictive value 5.26%. These results show that etap is a rather specific, although poorly sensitive predictor of overreaching but has no interest in the diagnosis of the overtraining syndrome itself.

Adult↗

PubMed2006

Hemorheologic effects of low intensity endurance training in sedentary patients suffering from the metabolic syndrome.

Hemorheologic effects of exercise training ("hemorheologic fitness") are very different according to the mode and the intensity of this training. We previously reported that low intensity endurance training in sedentary patients suffering from the metabolic syndrome sumultaneously improved blood rheology, body composition and lipid oxidation at exercise. We aimed at analyzing the link among these improvements in 24 patients submitted to a 2 months targeted training designed for increasing exercise lipid oxidation. Variations of whole blood viscosity at high shear rate (etab 1000 s(-1)) were explained here by two statistically independent determinants: hematocrit and red cell rigidity. etab decreased in 16 subjects, but increased in 8, due to a rise in hematocrit. Changes in RBC rigidity appeared to reflect weight loss and decrease in LDL cholesterol. Plasma viscosity was related to cholesterol and its training-induced changes are related to those of VO2 max ) but not to lipid oxidation. Red cell aggregability (Myrenne) reflected both the circulating lipids (Chol, HDL and LDL) and the ability to oxidize lipids at exercise. Factors associated to a post-training decrease in aggregability (M1) were weight loss and more precisely decrease in fat mass, improvement in lipid oxidation, rise in HDL-Chol, and decrease in fibrinogen. On the whole the major determinant of hemorheologic improvement was an increase in cardiorespiratory fitness (VO2 max ), correlated with a decrease in plasma viscosity, rather than an improvement in lipid metabolism, although RBC aggregability and deformability exhibited clear relationships with lipid metabolism. For which reason Hct increased in 30% of the patients during this kind of training remains unclear.

Aged↗

PubMed2005

Simvastatin induces impairment in skeletal muscle while heart is protected.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are widely used to reduce plasma cholesterol concentration. However, statins are also known to induce various forms of muscular toxicity. We have previously shown that acute application of simvastatin on human skeletal muscle samples induced a cascade of cellular events originating from mitochondria and resulting in a global alteration of Ca2+ homeostasis. The present study was designed to further define the origin of the mitochondria impairment and to understand the apparent lack of deleterious effect on the heart. Using fluorescence imaging analysis and oxygraphy on human and rat skinned skeletal muscle samples, we show that the simvastatin-induced mitochondria impairment results from inhibition of the complex I of respiratory chain. Similar simvastatin-induced mitochondria impairment and alteration of Ca2+ homeostasis occur in permeabilized but not in intact ventricular rat cardiomyocytes. In intact rat skeletal muscle fibers from the flexor digitorum brevis muscle, the simvastatin-induced alteration of Ca2+ homeostasis is abolished when monocarboxylate transporter (MCT4) is inhibited. The impairment of complex I by simvastatin might be the primary step of its cellular deleterious effects leading to muscle fiber death. This mechanism is seen specifically in skeletal muscles. This specificity should be in part attributed to a preferential uptake of statins by MCT4 that is not expressed in cardiomyocytes.

Animals↗

PubMed2005

Endurance training increases lactate transport in male Zucker fa/fa rats.

The purpose of this study was to investigate the effect of endurance training (10 weeks) on previously reported alterations of lactate exchange in obese Zucker fa/fa rats. We used sarcolemmal vesicles to measure lactate transport capacity in control sedentary rats, Zucker (fa/fa), and endurance trained Zucker (fa/fa) rats. Monocarboxylate transporter (MCT) 1 and 4 content was measured in sarcolemmal vesicles and skeletal muscle. Training increased citrate synthase activity in soleus and in red tibialis anterior, and improved insulin sensitivity measured by intraperitoneal glucose tolerance test. Endurance training increased lactate influx in sarcolemmal vesicles at 1 mM of external lactate concentration and increased MCT1 expression on sarcolemmal vesicles. Furthermore, muscular lactate level was significantly decreased after training in red tibialis anterior and extensor digitorum longus. This study shows that endurance training improves impairment of lactate transport capacity that is found in insulin resistance state like obesity and type 2 diabetes.

Amino Acid Sequence↗

PubMed2005

Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle.

Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, and fatigability) occur frequently. We hypothesized that the iatrogenic effects of statins could result from alterations in Ca(2+) homeostasis. Acute applications of simvastatin on human skeletal muscle fibers triggered a Ca(2+) wave of intra-cellular Ca(2+) that mostly originates from sarcoplasmic reticulum (SR) Ca(2+)-release. In addition, simvastatin increased mitochondrial NADH content and induced mitochondrial membrane depolarization (EC(50)=1.96 microM) suggesting an altered mitochondrial function. Consequently on simvastatin application, a weak mitochondrial Ca(2+) efflux (EC(50)=7.8 microM) through permeability transient pore and Na(+)/Ca(2+) exchanger was triggered, preceding the large SR-Ca(2+) release. Increased SR Ca(2+) content after acute application of statin is also suggested by the increased Ca(2+) spark amplitude and by the effect of cyclopiazonic acid. We thus conclude that simvastatin induced alterations in mitochondrial function which lead to an increase in cytoplasmic Ca(2+), SR-Ca(2+) overload, and Ca(2+) waves. Taken together, these statin-induced muscle dysregulations may contribute to myotoxicity.

Calcium↗

PubMed2005

Substrate oxidation during exercise at moderate and hard intensity in middle-aged and young athletes vs sedentary men.

This study investigated the combined effects of endurance training and aging on substrate oxidation during exercise. Thirty-one healthy male subjects in 4 groups (8 middle-aged trained cyclists, 8 young trained cyclists, 7 middle-aged sedentary men, and 8 young sedentary men) performed 2 50-minute cycle ergometer exercise tests, below and above (+/-15%) their individual ventilatory threshold (VT). Substrate oxidation was evaluated by indirect calorimetry during the steady-state tests. Aging decreased carbohydrate (CHO) use (P<.05) in all subjects regardless of fitness status or exercise intensity. However, it declined 2-fold less in the trained men (P<.05) and was associated with a stronger epinephrine response (P<.05). During hard-intensity exercise, endurance training increased by 100% CHO use in the older men (P<.05). In the younger men, training increased fat oxidation but did not change CHO oxidation, resulting in a marked decrease in the ratio between CHO and fat used at high-intensity exercise (-93%; P<.05). These data suggest an age-related decline in the use of CHO as an energy source in exercising men, independent of intensity level. This decline, however, is attenuated in well-trained men for exercise intensities above the VT. In view of these findings, we hypothesize that cycling training performed at a specific exercise intensity (ie, 15% above VT) may improve CHO mobilization and use in middle-aged men.

Adult↗

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

Limited accuracy of surrogates of insulin resistance during puberty in obese and lean children at risk for altered glucoregulation.

This study evaluated the accuracy of surrogate indexes of insulin sensitivity (SI) in children. Surrogates (homeostasis model assessment index of insulin resistance, quick insulin sensitivity index, and 40/insulin ratio index) were cross-sectionally investigated in 66 obese and lean children (17 Tanner stage I, 19 Tanner stage II-III, and 30 Tanner stage IV-V) as indexes of insulin resistance in comparison with the minimal model. The pubertal decrease in SI was found with the minimal model (-47%; P = 0.01), but not with surrogates, which were not correlated to SI. Baseline insulin (Ib) did not mirror the decrease in SI, did not significantly change when plotted against pubertal stage or age, and was not correlated to SI. Ib and surrogates were positively correlated with the body mass index. The disposition index, which quantifies the feedback between SI and insulin release, was widely scattered and decreased during puberty (P = 0.05). The specificity and sensitivity of surrogates as predictors of insulin resistance were poor (e.g. 81.1% and 30.7%, respectively, for the homeostasis model assessment index of insulin resistance). Thus, during puberty, surrogates are not accurate predictors of insulin resistance. Because reference methods are rather expensive and invasive, additional studies of alternative techniques for evaluating SI are needed to allow accurate measurement of insulin resistance in children.

Adolescent↗

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↗