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M Laville

Publications and source records attributed to M Laville.

At least 37 records · Page 2Linked to original sources
PubMed2002

Molecular mechanisms of insulin-stimulated glucose uptake in adipocytes.

The stimulation of muscle and adipose tissue glucose metabolism, which is ultimately responsible for bringing about post-absorptive blood glucose clearance, is the primary clinically relevant action of insulin. Insulin acts on many steps of glucose metabolism, but one of the most important effects is its ability to increase the rate of cellular glucose transport. This results from the translocation of the insulin-responsive transporter isoform, GLUT4, from intra-cellular vesicular storage sites to the plasma membrane. In adipocytes, a substantial amount of cellular GLUT4 is located in a specific highly insulin-responsive storage pool, termed GLUT4 Storage Vesicles (GSVs). GLUT4 can also translocate to the plasma membrane from the recycling endosomal pool which also additionally contains the GLUT1 isoform of glucose transporter and the transferrin receptor. In this article we review the molecular mechanism by which insulin stimulates GLUT4 translocation in adipose cells, including the nature of the signaling pathways involved and the role of the cytoskeleton.

Adipocytes↗
PubMed2001

Expression of the splice variants of the p85alpha regulatory subunit of phosphoinositide 3-kinase in muscle and adipose tissue of healthy subjects and type 2 diabetic patients.

The regulation by insulin of the expression of the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase) is impaired in skeletal muscle and adipose tissue of type 2 diabetic patients. The gene encoding p85alpha (named grb-1) can generate several variants by alternative splicing, all being able to activate the p110 catalytic subunits of PI 3-kinase. Our aims were (i) to determine the mRNA expression profiles of these variants in human skeletal muscle and adipose tissue; (ii) to investigate the effect of insulin on their expression in vivo and in vitro in muscle and (iii) to verify whether this regulation is defective in type 2 diabetes. We determined the human genomic organization of grb-1 and set up reverse transcriptase competitive PCR assays for the quantification of each mRNA variant. In muscle, p85alpha and p50alpha mRNAs were the most abundant, and p55alpha represented less than 20% of all grb-1-derived mRNAs. In adipose tissue, p85alpha was expressed predominantly and p55alpha mRNA was not detectable. These expression profiles were not different in type 2 diabetics. During a 3 h hyperinsulinaemic clamp, insulin increased the mRNA expression of the three variants in muscle of control subjects. In diabetic patients, the effect of insulin on p85alpha and p50alpha mRNAs was blunted, and largely reduced on p55alpha transcripts. In cultured human myotubes, up-regulation of p85alpha, p55alpha and p50alpha mRNAs by insulin was abolished by LY294002 (10 microM) and by rapamycin (50 nM), suggesting that the PI 3-kinase/protein kinase B/p70 S6 kinase pathway could be involved in the stimulation of grb-1 gene expression by insulin in human muscle cells.

Adipose Tissue↗
PubMed2001

Chronic renal disease.

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

[Hypertensive nephropathy: a growing cause of renal insufficiency].

KIDNEY DISEASE AND HYPERTENSION: Hypertension is increasingly associated to renal insufficiency leading to end stage renal damage (ESRD), through several mechanisms involving renal vasculature. Ten to 25% of new ESRD patients are now categorized as hypertensive nephropathy and vascular renal disease. EPIDEMIOLOGY IN FRANCE: Besides the risk of spontaneously evolving atheromatous stenoses of renal arteries, the individual risk of ESRD in essential hypertension is relatively low, except in selected genetic backgrounds such as black people especially in the USA. In long term studies, the risk of ESRD in treated hypertensives is between 1.5 and 3% at 15 years, and approximately 3% of French hypertensives have plasma creatinine levels above 150 mumol/l. The risk of significant creatinine increase is doubled each 20 mmHg increment in diastolic BP, but long term studies suggest that the influence of systolic BP is even greater. PERSPECTIVES: Animal models have extended our pathophysiological view of hypertensive nephropathy, in which renal ischemia and nephron loss will induce preglomerular vasodilation and glomerular hypertension. In the future, the evaluation of the renal prognosis in essential hypertension could benefit from indirect renal hemodynamic explorations, genetic progress, determination of microalbuminuria which is the renal probe of a more generalized microvascular disease, these indices should be useful to adapt the antihypertensive therapy, with the goal of normalizing blood pressure at a lowest albumin excretion rate.

Age Distribution↗
PubMed2001

The expression of the p85alpha subunit of phosphatidylinositol 3-kinase is induced by activation of the peroxisome proliferator-activated receptor gamma in human adipocytes.

AIMS/HYPOTHESIS: Thiazolidinediones are new oral antidiabetic drugs that activate the nuclear receptor PPARgamma. Our aim was to identify potential target genes of PPARgamma in the human adipocyte in order to clarify how thiazolidinediones improve insulin sensitivity. METHODS: The effect of BRL 49653 (Rosiglitazone) on the mRNA expression of insulin receptor, insulin receptor substrate-1, p85alpha, p110alpha and p110beta subunits of phosphatidylinositol 3-kinase, Glut 4 and hormone sensitive lipase was examined in isolated adipocytes. Target mRNA levels were determined by RT-competitive PCR. RESULTS: The BRL 49653 (1 micromol/l) increased the mRNA concentrations of p85alphaPI-3 K (264 +/- 46 vs 161 +/- 31 amol/microg total RNA, p = 0.003) whithout affecting the expression of the other mRNAs of interest. This effect was dose-dependent (K0.5 = 5 nmol/l) and was reproduced by a specific activator of RXR, indicating that it was probably mediated by the PPARgamma/RXR heterodimer. The BRL 49653 also increased the amount of p85alphaPI-3K protein in adipose tissue explants (71 +/- 19%). In addition, BRL 49653 produced a more than twofold increase in insulin stimulation of phosphatidylinositol 3-kinase activity and significantly enhanced the antilipolytic action of insulin. CONCLUSION/INTERPRETATION: This work demonstrates that the gene of p85alphaPI-3K is probably a target of PPARgamma and that thiazolidinediones can improve insulin action in normal human adipocytes. Although the precise mechanism of action of BRL 49653 on PI3-Kinase activity is not completely clear, these findings improve our understanding of the insulin-sensitizing effects of the thiazolidinediones, possible drugs for the treatment of Type II (non-insulin-dependent) diabetes mellitus.

Adipocytes↗
PubMed2001

Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study.

The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.

Aged↗
PubMed2001

Total-body-water measurement with (18)O-labeled water in short-bowel patients with an ileostomy.

The aim of this study was to evaluate the use of H(2)(18)O for total-body-water (TBW) determination in patients with short bowel because ileostomy losses of labeled water can falsify TBW. Thirteen adult short-bowel patients were studied after an overnight fast. Saliva, blood, urine and ileostomy output were collected before and 30, 60, 90, 120, 240, and 360 min after oral ingestion of 0.88 g/kg of 2.5% H(2)(18)O to measure (18)O abundance by isotope-ratio mass spectrometry. TBW was calculated from the dilution of the isotopic water in saliva and plasma. The quantity of labeled water lost in the ileostomy was calculated from the isotopic enrichment of the ileostomy output from T0 to T360. The values obtained from saliva or plasma with (corrected) and without (uncorrected) considering H(2)(18)O lost in the ileostomy output were compared with a paired t test. Agreement was evaluated using the Bland-Altman method. From T0 to T360, the ileostomy output and the percentage of lost labeled water were 490 +/- 314 mL and 6.38 +/- 8.52%, respectively. TBW calculated from plasma or saliva isotopic enrichment was different, and a significant difference was also observed between corrected and uncorrected TBW values (saliva: uncorrected TBW = 32.35 +/- 7.52 L, corrected TBW = 30.29 +/- 6.09 L; plasma; uncorrected TBW = 30.80 +/- 7.29 L, corrected TBW = 28.79 +/- 5.79 L). The agreement between the values obtained from the two dilution spaces or between the two calculation methods was poor. Because of the large discrepancies between calculation methods, determination of TBW from oral ingestion of (18)O-labeled water in patients with short bowel should be calculated only from plasma (18)O space dilution and should consider ileostomy losses.

Body Water↗
PubMed2001

Simultaneous validation of ten physical activity questionnaires in older men: a doubly labeled water study.

OBJECTIVE: The purpose of this study was to simultaneously validate 10 physical activity (PA) questionnaires in a homogenous population of healthy elderly men against the reference method: doubly labeled water (DLW). DESIGN: Cross-sectional study. SETTING: Community-based sample from Lyon, France. PARTICIPANTS: Nineteen healthy old men (age 73.4 +/- 4.1 years), recruited from various associations for elderly people in Lyon, agreed to participate in the study. MEASUREMENTS: The questionnaire-derived measures (scores) were compared with two validation measures: DLW and maximal oxygen uptake (VO2max). With the DLW method three parameters were calculated: (1) total energy expenditure (TEE), (2) physical activity level (PAL), i.e., the ratio of TEE to resting metabolic rate, (3) energy expenditure of PA. RESULTS: Relative validity. Correlation between the questionnaires and TEE ranged from 0.11 for the Yale Physical Activity Survey (YPAS) total index to 0.63 for the Stanford usual activity questionnaire. This questionnaire also gave the best correlation coefficients with PAL (0.75), and with VO2max (0.62). Significant results with TEE measured by the DLW method were also obtained for college alumni sports score, Seven Day Recall moderate activity, and Questionnaire d'Activité Physique Saint-Etienne sports activity (r = 0.54, r = 0.52, and r = 0.54, respectively). Absolute validity. No difference was found between PA measured by the Seven Day Recall or by the YPAS and DLW, on a group basis. The limits of agreement were wide for all the questionnaires. CONCLUSIONS: Only a few questionnaires demonstrated a reasonable degree of reliability and could be used to rank healthy older men according to PA. Correlation coefficients were best when the Stanford Usual Activity Questionnaire was compared with all the validation measures. The two questionnaires reporting recent PA, the Seven Day Recall, and YPAS accurately assessed energy expenditure for the group. The individual variability was high for all the questionnaires, suggesting that their use as a proxy measure of individual energy expenditure may be limited.

Activities of Daily Living↗
PubMed2001

Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients.

Nutritional factors and dialysis adequacy are associated with outcome in hemodialyzed patients, but their relative contribution remains controversial, particularly when dialysis adequacy complies with current recommendations (Kt/V >1.2). Survival, clinical, and nutritional data from a cohort of prevalent 1,610 patients treated by hemodialysis in 20 centers in France have been collected over a 2.5-year period, from January 1996 to July 1998. Data including age, sex, cause of end-stage renal disease (ESRD), clinical outcome, time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were analyzed. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) from creatinine generation were computed from pre- and postdialysis urea and creatinine levels. The characteristics of the patients were as follows: age 59.6 +/- 16.5 years, 58.8% males, 11% of diabetics, time on dialysis 63.2 +/- 64.5 m. Weekly dialysis time was 12.18 +/- 1.78 hrs, Kt/V 1.34 +/- 0.34, nPCR 1.10 +/- 0.35 g/kg body weight/day. Albumin concentration was 39.4 +/- 5.3 g/L, prealbumin was 0.33 +/- 0.09 g/L, BMI was 23.0 +/- 4.5 kg/m(2). Overall survival was 89.7% +/- 0.8% and 78.4% +/- 1.1% after 1 and 2 years. In the Cox proportional hazard model, survival was significantly influenced by age, the presence of diabetes, and by concentrations of albumin and prealbumin, but not by other variables, including Kt/V and urea reduction ratio. These results indicate that nutritional protein concentrations were predictive of dialysis outcome, whereas variables reflecting actual body composition and dialysis dose were not. Furthermore, in this well-dialyzed population, dialysis adequacy had no influence on survival. In conclusion, when adequacy targets are met in hemodialyzed patients, survival is mainly dependent on age and nutritional status. Efforts should be focused on the most efficient ways to maintain nutritional status in these patients.

Adult↗
PubMed2001

Influence of dietary fat on postprandial glucose metabolism (exogenous and endogenous) using intrinsically (13)C-enriched durum wheat.

The present study evaluates the influence of different amounts of fat added to starch on postprandial glucose metabolism (exogenous and endogenous). Nine women (24 (se 2) years old, BMI 20.4 (se 0.7) kg/m(2)) ingested 1 week apart 75 g glucose equivalent of (13)C-labelled starch in the form of pasta without (low fat; LF) or with 15 (medium fat; MF) or 40 (high fat; HF) g sunflower oil. During the 7 h following meal consumption, plasma glucose, non-esterified fatty acids, triacylglycerols (TG) and insulin concentrations, and endogenous (using [6,6-(2)H(2)]glucose) and exogenous glucose turnover were determined. With MF and HF meals, a lower postprandial glucose peak was observed, but with a secondary recovery. A decrease in exogenous glucose appearance explained lower glycaemia in HF. At 4 h after the HF meal the insulin, insulin:glucose and postprandial blood TG were higher than those measured after the LF and MF meals. Despite higher insulinaemia, total glucose disappearance was similar and endogenous glucose production was suppressed less than after the LF and MF meals, suggesting insulin resistance. Thus, the addition of a large amount of fat appears to be unfavourable to glucose metabolism because it leads to a feature of insulin resistance. On the contrary, the MF meal did not have these adverse effects, but it was able to decrease the initial glycaemic peak.

Adult↗
PubMed2001

Haemodialysis with the biocompatible high permeability AN-69 membrane does not alter plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3.

BACKGROUND: Insulin-like growth factor-I (IGF-I) bioactivity has been reported to be decreased in maintenance haemodialysis patients and this may affect their nutritional status. Clearances of IGF-I and its binding proteins (IGFBPs) during haemodialysis sessions using a high permeability biocompatible membrane are unknown. METHODS: Five well nourished, non-diabetic adult patients were studied during one 4-h morning haemodialysis treatment using the high permeability biocompatible AN-69 dialyser. Blood was collected at the arterial and venous ports of the dialyser at 0, 1, 2 and 4 h of dialysis for haematocrit, plasma IGF-I, IGFBP-3 and insulin measurements. IGF-I, IGFBP-3 and insulin concentrations were adjusted for haemoconcentration before comparisons were made. RESULTS: At the beginning of the dialysis session, plasma IGF-I, IGFBP-3 and insulin levels were within the normal range (297 +/- 47 ng/ml (mean+/-SEM), 4.3 +/- 0.6 microg/ml and 11.8 +/- 3.4 microIU/ml, respectively). During the session, insulin tended to be cleared through the dialyser, whereas plasma IGF-I and IGFBP-3 values did not vary significantly. CONCLUSION: Dialysis with the high permeability AN69 membrane did not alter the main blood compounds of the IGF system in well nourished chronic haemodialysis patients, and it is unlikely that the malnutrition frequently observed in such patients would result from alterations of the IGF system during haemodialysis.

Acrylic Resins↗
PubMed2001

Perceived job stress but not individual cardiovascular reactivity to stress is related to higher blood pressure at work.

Psychological stress has been reported to be related to higher blood pressure (BP) and unfavorable cardiovascular profile. However, because of the complexity of personal stress management, a multilevel stress measurement strategy is needed. The aim of this cross-sectional study was to analyze the respective influences of the subjective perception of professional strain (high demand and low latitude) and cardiovascular reactivity to a stress test (Stroop stress test) on BP. Worksite BP was measured in 303 healthy normotensive subjects, 18 to 55 years of age, who worked in the same chemical company. In a subset of 70 randomly selected subjects, 24-hour ambulatory BP was performed to assess BP during working hours. The 20% of subjects who reported the highest job strain (high-strain group) or the highest BP stress reactivity (high-responder group) were compared with the remaining subjects (80%) (non-high-strain or low-responder groups). Subjects who submitted to the highest job strain had significantly higher ambulatory diastolic BP (4.5 mm Hg, P=0.015) during only working hours, whereas BP was similar during the remaining hours. Worksite BP and stress cardiovascular reactivity were similar between job strain groups. BP stress reactivity did not influence worksite and ambulatory BP. Spontaneous BP variability assessed by standard deviation and spectral analysis was equivalent between complementary groups. Prevalence of microalbuminuria was significantly higher in the high-responder group (8.2% versus 2.5% in low responders) and only slightly higher in the high-strain group (6.2% versus 3.2% in non-high strain). Potential confounding factors, such as age, gender, alcohol consumption, salt intake, body mass index, and occupation, which were equivalent between groups, did not interfere with our results. Our study quantifies high-professional strain effects on BP levels that appear to be higher only during the working period and to be independent from spontaneous BP variability and stress BP reactivity.

Adolescent↗
PubMed2001

Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes.

Defective regulation of gene expression may be involved in the pathogenesis of type 2 diabetes. We have characterized the concerted regulation by insulin (3-h hyperinsulinemic clamp) of the expression of 10 genes related to insulin action in skeletal muscle and in subcutaneous adipose tissue, and we have verified whether a defective regulation of some of them could be specifically encountered in tissues of type 2 diabetic patients. Basal mRNA levels (determined by reverse transcriptase-competitive polymerase chain reaction) of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, GLUT4, glycogen synthase, and sterol regulatory-element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17), type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9) subjects. In muscle, the expression of hexokinase II was decreased in type 2 diabetic patients (P < 0.01). In adipose tissue, SREBP-1c (P < 0.01) mRNA expression was reduced in obese (nondiabetic and type 2 diabetic) subjects and was negatively correlated with the BMI of the subjects (r = -0.63, P = 0.02). Insulin (+/-1,000 pmol/l) induced a two- to threefold increase (P < 0.05) in hexokinase II, p85alphaPI3K, and SREBP-1c mRNA levels in muscle and in adipose tissue in control subjects, in insulin-resistant nondiabetic obese patients, and in hyperglycemic type 1 diabetic subjects. Upregulation of these genes was completely blunted in type 2 diabetic patients. This study thus provides evidence for a specific defect in the regulation of a group of important genes in response to insulin in peripheral tissues of type 2 diabetic patients.

Adipose Tissue↗