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Biomedical subjects

J Mercier

Publications and source records attributed to J Mercier.

At least 55 records · Page 3Linked to original sources
PubMed2001

Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise.

Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise-induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphasize the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects.

Blood Glucose↗
PubMed2001

Insulin and non-insulin-dependent glucose disposal in middle-aged and young athletes versus sedentary men.

The purpose of this study was to delineate the respective roles of aging and endurance training on glucose disposal. 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. After overnight fasting, glucose was administered intravenously (0.5 g. kg(-1), 30% solution) and insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness (Sg) using Bergman's minimal model. Sg includes basal insulin effectiveness (BIE) and glucose effectiveness at zero insulin (GEZI). Endurance training improved SI and Sg in all subjects, regardless of age (P <.05), but an increase in GEZI was found only in young men (P <.05). An effect of aging was found in sedentary subjects, who exhibited a lower SI (P <.05) when older. However, this effect disappeared with training, in which SI was nearly identical in young and middle-aged subjects. There was a correlation between SI and &Vdot;omicron(2max) in middle-aged men (r =.76, P <.01). These data suggest that the higher glucose uptake in endurance-trained male cyclists was mostly attributable to an increase in non-insulin-dependent glucose uptake in the young men and to an increase in its insulin-dependent component in the middle-aged men.

Adult↗
PubMed2001

Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport.

Impaired lactate metabolism is a metabolic disorder, which is not fully understood in the diabetic state including streptozotocin (STZ)-induced diabetes. We investigated whether STZ-induced diabetes results in altered lactate exchanges using the rat muscle sarcolemmal vesicles (SV) model. Fifteen days after diabetes onset (1 STZ-injection, 65 mg/kg, intraperitoneal [IP]), rats had higher blood and muscle lactate concentrations compared with normal rats (1.50 +/- 0.09 v 1.95 +/- 0.21 mmol/L (not significant [NS]) and 21.02 +/- 1.26 v 25.53 +/- 0.98 mmol/kg wet weight (ww); P < .05). The initial rate of lactate uptake was measured at various external lactate concentrations using SV of both group in zero-trans conditions. STZ-induced diabetes decreased the initial rate of total lactate influx at external lactate concentrations from 1 to 100 mmol/L (P < .05). This decrease in lactate transport was found in addition to an increased free radical production, as indicated by a significant increase in malonedialdehyde (MDA) concentration (64.3 +/- 8.7 v 100.3 +/- 13.5 nmol. g(-1) ww, P < .05), coupled with a higher glutathione peroxidase (Gpx) activity (48.03 +/- 3.13 v 84.7 +/- 15.01 micromol. min(-1). mg(-1) protein, P < .05) in red gastrocnemius. We concluded that STZ-induced diabetes decreases total lactate transport activity in rat SV and is associated with increased muscular oxidative stress.

Animals↗
PubMed2001

Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS; MIM SACS 270550) is frequent in northeastern Québec. Two causal mutations have been identified in the 11.7-kb single exon sacsin gene by sequence-based analyses. Mutation g.6594delT (DeltaT) was reported in 96% of the patients whereas a g.5254C --> T nonsense mutation has been observed only in 2 families. Here we report a reliable and inexpensive method to detect more than 95% of the ARSACS disease alleles from northeastern Québec using allele-specific oligonucleotide (ASO) hybridization. This procedure is being incorporated into the diagnosis of ARSACS, as well as being used for carrier detection in at-risk families from northeastern Québec.

Alleles↗
PubMed2001

RNA trafficking signals in human immunodeficiency virus type 1.

Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.

Animals↗
PubMed2001

Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats.

The present experiments were undertaken to characterize 1) the hindlimb muscle mass lactate uptake and 2) the expression of monocarboxylate transporter isoforms MCT1 and MCT4, as well as lactate dehydrogenase (LDH) isozyme distribution, in various skeletal muscles of Zucker fa/fa rats taken as a model of insulin resistance-related obesity. Initial lactate uptake at six different concentrations was measured in sarcolemmal vesicles (SV) by use of L-[U-(14)C]lactate. Compared with controls, the maximal rate of lactate uptake and affinity were decreased in SV of Zucker rats (approximately 30%) in which MCT4 content was significantly decreased (P < 0.05). MCT4 expression was decreased in soleus, extensor digitorum longus, and red tibialis anterior (RTA; P < 0.05), but not in white tibialis anterior, whereas MCT1 expression was decreased only in RTA of Zucker rats (P < 0.05). Obesity led to a shift toward type M-LDH isozyme in mixed muscles. We conclude that obesity leads to changes in muscular MCT1 and MCT4 expression, which, when associated with LDH isozyme redistribution, may contribute to the hyperlactatemia noted in insulin resistance.

Animals↗
PubMed2001

Effect of hydration on exercise-induced growth hormone response.

DESIGN: Growth hormone (GH) has demonstrated water-retaining effects in subjects at rest, whereas other research has indicated that GH may stimulate sweating. Thus, the aim of this study was to investigate the effect of fluid intake on the exercise-induced GH response. METHODS: Seven healthy male volunteers (age: 27.4+/-1.3 years, weight: 74.5+/-1.1 kg, height: 179.3+/-2.3 cm) performed a 40-min submaximal rectangular cycling exercise in two different sessions. The first session (Session 1) was performed without water intake, and the second (Session 2) involved the ingestion of spring water (four intakes) corresponding to the volume of water lost during the first session. RESULTS: In session 1, the water loss was 568+/-32 ml. In Session 2, the volume of water loss was not significantly different from the volume of fluid intake (524+/-16 versus 568+/-32 ml respectively). The decrease in plasma volume was significantly reduced in Session 2 (-6.69+/-1.59% versus -11.3+/-1.89%; P<0.05). In Session 1, the GH concentration was significantly lower than that during Session 2 after 25 min (3.04+/-1.05 versus 5.26+/-1.81; P<0.05) and after 40 min (13.7+/-3.55 versus 17.60+/-4.14 ng/ml; P<0.05) of exercise. The total GH response was significantly lower in Session 1 than in Session 2 (136.6+/-39.2 versus 202.4+/-58.9 ng/ml x min; P<0.05). CONCLUSIONS: We conclude that the exercise-induced GH response decreases when exercise is performed without fluid intake.

Adult↗
PubMed2001

Exercise hypoglycemia in nondiabetic subjects.

Hypoglycemia during exercise is a common event due to an unbalance between training volume, nutrition, and external influences such as chronobiology, temperature or altitude, in subjects characterized by an acute and chronic increase in glucose effectiveness and insulin sensitivity. While it is preventable by adequate pre-exercise feeding with carbohydrates, it can also be induced by a prior carbohydrate meal with high glycemic index. Adequate training induces resistance to hypoglycemia via a shift in the balance of oxidized substrates and marked hormonal adaptations, but overtraining, by partially reversing this adaptation, favorizes hypoglycemia. Exercise hypoglycemia is a cause of fatigue or exercise cessation, but also impairs thermoregulatory adaptation and is assumed to fragilize muscles and tendons for traumatic events.

Dietary Carbohydrates↗
PubMed2001

Balance of substrate oxidation during submaximal exercise in lean and obese people.

OBJECTIVES: To compare fat and carbohydrate oxidation at different exercise intensities between overweight and normal-weight subjects, in order to analyze the influence of muscular metabolic abnormalities in obese people on substrate utilization during exercise. MATERIAL AND METHODS: 32 healthy sedentary overweight subjects (Body Mass Index (BMI): 30.8 +/- 0.8 kg/m(2); body fat: 37.4 +/- 1.1%; mean +/- SEM) and 26 controls (BMI: 23 +/- 0.4 kg/m(2); body fat: 22.7 +/- 1.1%) matched for age and sex were examined. The test consisted in four six-min. submaximal steady-state workloads with calculation of substrate oxidation rates and derived quantitative parameters, i.e., crossover point (defined as the power at which carbohydrate-derived energy becomes predominant) and maximal fat oxidation rate point. In addition, the accuracy of the test was analyzed and was found to be satisfactory. RESULTS: While exercise intensities were similar in both group, fat oxidation rates were significantly lower in overweight group (p<0.05). The crossover and the maximal fat oxidation rate points were significantly lower in overweight subjects than in controls: 33.3 +/- 2 vs 50.1 +/- 3.4% and 30.5 +/- 2.3 vs 44.6 +/- 3.3% of maximal aerobic power, respectively (p<0.001). CONCLUSION: Sedentary overweight subjects, compared to controls at the same exercise intensities, exhibited an alteration of the balance of substrate oxidation, reflected by lower rates of fat oxidation and a shift of quantitative parameters to lower intensities. The test appeared to be reliable and could be of interest to advise an individualized exercise prescription in obese people.

Adult↗
PubMed2001

Multivariate analysis of relationships between insulin sensitivity and blood rheology: is plasma viscosity a marker of insulin resistance?

We previously reported in populations exhibiting all the spectrum of insulin sensitivity (SI) values correlations between SI and blood viscosity eta suggesting that high eta is an additional symptom of the insulin resistance syndrome. However, due to the elevation of insulinemia (I) which is usually associated with insulin resistance it remained to determine whether this relationship was explained by SI or I. We analyzed SI with the minimal model procedure in 108 nondiabetic subjects and analyzed correlations of SI with blood rheology (eta, RBC aggregation and rigidity). Across quartiles of SI (defined after log transformation since distribution of SI was not normal), hematocrit and red cell rigidity remained stable, while aggregability and plasma viscosity (etap) increased in the lowest quartile. SI was correlated to only two rheological parameters: etap (r= -0.280, p=0.005) and Myrenne index M1 (r= -0.219, p=0.044). Among SI, I, age and BMI multivariate analysis selected only BMI as a determinant of either whole blood viscosity (etawb: r= -0.301, p=0.004) and RBC disaggregation threshold (gammaD: r= -0.331, p=0.013), only I as determinant of M1 (r=0.254, p=0.03), and a combination of BMI (p=0.009) and SI (p=0.007) for etap. Although age and obesity are factors of hyperviscosity, the hemorheological disturbances found in insulin resistance are not fully statistically "explained" by those two factors. While hyperaggregability (measured with M1) is rather related to hyperinsulinism, etap is influenced by SI and should be further investigated as a simple marker for the follow up of insulin-resistant states.

Adult↗
PubMed2001

[Maximal oxygen uptake in healthy children: factors of variation and available standards].

Aerobic physical fitness, in children, is assessed by measurement of the maximal oxygen consumption during exercise testing. Representative norms of the studied population are required for interpretation. The aim of this article is to specify and review the available VO2max norms and factors of variation, including: sex, anthropometric characteristics (height, lean body mass and weight) and physical activity level. Ideally, VO2max norms should include lean body mass and physical activity with an allometric equation. Since such norms do not exist today, interpretation remains difficult. In France, the must satisfactory norms for non trained children include body mass without an allometric equation (boys: 47 +/- 2 ml.mn.-1 kg-1, girls: 40 +/- 3 ml.mn.-1 kg-1 with a post puberty decrease). Further studies on VO2max norms that include lean body mass and a physical activity questionnaire are required to improve exercise test interpretation in children.

Body Height↗
PubMed2000

Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.

North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.

Adult↗
PubMed2000

Relationships between fibrinogen and insulin resistance.

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m(2) and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min(-1)/(microU/ml)x10(-4), covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=-0.76,P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56,P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-alpha, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.

Adult↗
PubMed2000

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.

Amino Acid Sequence↗
PubMed2000

Influence of lesion level on the cardioventilatory adaptations in paraplegic wheelchair athletes during muscular exercise.

OBJECTIVES: To characterize the influence of neurological lesion level on the cardiorespiratory and ventilatory responses of two groups of paraplegic athletes during incremental exercise on a treadmill and in the usual conditions for wheelchair exercise. METHODS: Cardioventilatory responses evaluated in two groups of paraplegic wheelchair sportsmen designated as high paraplegic athletes (HPA) and low paraplegic athletes (LPA). After 2 min of data collection at rest and 3 min of warm-up at 4 km x h(-1), treadmill speed was increased by 1 km x h(-1) every minute until exhaustion. During this test, ventilation and its components, as well as respiratory exchanges, were measured breath by breath (C.P.X. Medical Graphics) every minute by taking the mean of the last 20 s of each increment. RESULTS: Spirometric values presented no significant differences between groups. At rest, no significant difference was observed between the two groups for all cardiorespiratory and ventilatory values obtained during the treadmill test. At submaximal exercise, all variables increased with the augmentation in workload. With the exception of R, there were no significant differences in the classic cardiorespiratory parameters (VO2, VCO2, HR, VE) between the two groups of paraplegics. For the ventilatory parameters, we observed significant differences between the two groups, with values of f and It/Trf significantly higher (0.01<P<0.001) and values of Trf and Vt significantly lower (0.01<P<0.001) for HPA versus LPA. We observed changes in breathing pattern, ie, in f, Vt, Trc and It/Trc, were significantly different between groups, with significantly higher values of f and It/Trc for HPA. We noted a ventilatory disturbance which was manifested by values of breathing frequency and tidal volume during exercise that were significantly different between groups. During maximal exercise, we observed no significant differences between the two groups concerning cardiorespiratory and ventilatory values. Despite the absence of significant differences, the more linear time course of the ensemble of HPA flows, the achievement of a greater number of work loads, and the higher maximal values indicate a better capacity for adaptation to exercise in the group of lower thoracic paraplegics. CONCLUSION: These results raise questions about the influence of neurological level and further research is needed to define with more precision the capacities of readaptation of the different cardiovascular and respiratory functions, as well as the training methods best adapted to the optimization of physical capacities.

Adaptation, Physiological↗