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Martine Laville

Publications and source records attributed to Martine Laville.

At least 19 recordsLinked to original sources
PubMed2006

Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs.

In the present study, we aimed to decipher the mechanisms involved in the transcriptional effect of insulin on the SREBP-1c specific promoter of the human srebf-1 gene. Using luciferase reporter gene constructs in HEK-293 cells (human embryonic kidney cells), we demonstrated that the full effect of insulin requires the presence of SREs (sterol response elements) in the proximal region of the promoter. Furthermore, insulin increases the binding of SREBP-1 (sterol-regulatory-element-binding protein-1) to this promoter region in chromatin immunoprecipitation assay. We also found that the nuclear receptors LXRs (liver X receptors) strongly activate SREBP-1c gene expression and identified the LXRE (LXR-response element) involved in this effect. However, our results suggested that these LXREs do not play a major role in the response to insulin. Finally, using expression vectors and adenoviruses allowing ectopic overexpressions of the human mature forms of SREBP-1a or SREBP-1c, we demonstrated the direct role of SREBP-1 in the control of SREBP-1c gene expression in human skeletal-muscle cells. Altogether, these results strongly suggest that the SREBP-1 transcription factors are the main mediators of insulin action on SREBP-1c expression in human tissues.

Adipose Tissue↗
PubMed2006

Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women.

BACKGROUND: Adiponectin, an adipocytokine secreted by adipose tissue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk factors for endometrial cancer. METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition to examine the relation between prediagnostic plasma adiponectin levels and endometrial cancer risk. Among pre- and postmenopausal women who were not currently using exogenous hormones, 284 women developed incident endometrial cancer during an average of 5.1 yr of follow-up. Using risk set sampling, 548 control subjects were selected, matched on center, age, menopausal status, phase of menstrual cycle, time of blood draw, and fasting status. Conditional logistic regression models were used to estimate relative risks and 95% confidence intervals. RESULTS: Adiponectin levels were inversely associated with endometrial cancer risk [body mass index-adjusted relative risk for the top vs. bottom quartile = 0.56 (95% confidence interval 0.36-0.86), P(trend) = 0.006]. There was evidence of a stronger inverse association among obese women than among nonobese women (P(heterogeneity) = 0.03). The inverse association also appeared stronger for women who were postmenopausal or perimenopausal than premenopausal at baseline, but this was not statistically significantly heterogeneous (P(heterogeneity) = 0.51). The association remained statistically significant after separate adjustment for other obesity-related physiological risk factors such as C-peptide, IGF binding protein-1, IGF binding protein-2, SHBG, estrone, or free testosterone but only marginally statistically significant after simultaneous adjustment for these factors. CONCLUSIONS: High circulating adiponectin levels are associated with reduced endometrial cancer risk, largely independent of other obesity-related risk factors.

Adiponectin↗
PubMed2006

Effect of physical inactivity on the oxidation of saturated and monounsaturated dietary Fatty acids: results of a randomized trial.

OBJECTIVES: Changes in the way dietary fat is metabolized can be considered causative in obesity. The role of sedentary behavior in this defect has not been determined. We hypothesized that physical inactivity partitions dietary fats toward storage and that a resistance exercise training program mitigates storage. DESIGN: We used bed rest, with randomization to resistance training, as a model of physical inactivity. SETTING: The trial took place at the Space Clinic (Toulouse, France). PARTICIPANTS: A total of 18 healthy male volunteers, of mean age +/- standard deviation 32.6 +/- 4.0 y and body mass index 23.6 +/- 0.7 kg/m(2), were enrolled. INTERVENTIONS: An initial 15 d of baseline data collection were followed by 3 mo of strict bed-rest alone (control group, n = 9) or with the addition of supine resistance exercise training every 3 d (exercise group, n = 9). OUTCOME MEASURES: Oxidation of labeled [d(31)]palmitate (the main saturated fatty acid of human diet) and [1-(13)C]oleate (the main monounsaturated fatty acid), body composition, net substrate use, and plasma hormones and metabolites were measured. RESULTS: Between-group comparisons showed that exercise training did not affect oxidation of both oleate (mean difference 5.6%; 95% confidence interval [95% CI], -3.3% to 14.5%; p = 0.20) and palmitate (mean difference -0.2%; 95% CI, -4.1% to 3.6%; p = 0.89). Within-group comparisons, however, showed that inactivity changed oxidation of palmitate in the control group by -11.0% (95% CI, -19.0% to -2.9%; p = 0.01) and in the exercise group by -11.3% (95% CI, -18.4% to -4.2%; p = 0.008). In contrast, bed rest did not significantly affect oleate oxidation within groups. In the control group, the mean difference in oleate oxidation was 3.2% (95% CI, -4.2% to 10.5%; p = 0.34) and 6.8% (95% CI, -1.2% to 14.7%; p = 0.08) in the exercise group. CONCLUSIONS: Independent of changes in energy balance (intake and/or output), physical inactivity decreased the oxidation of saturated but not monounsaturated dietary fat. The effect is apparently not compensated by resistance exercise training. These results suggest that Mediterranean diets should be recommended in sedentary subjects and recumbent patients.

Journal Article↗
PubMed2006

Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa.

Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565 +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day) and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/- 2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/- 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT.

Adipose Tissue↗
PubMed2006

Short-term activation of peroxysome proliferator-activated receptor beta/delta increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic patients.

Defective fatty acid oxidation in skeletal muscle is one of the possible causes of insulin resistance. Peroxisome proliferator-activated receptor beta activators are strong inducers of fatty acid oxidation. The aim of this study was to verify whether activation of fatty acid oxidation by PPARbeta agonists in human skeletal muscle cells prepared from type 2 diabetic patients could improve the reduced responses to insulin that characterized this cell model. GW0742 (10 nM) significantly increased fatty acid oxidation and oxidative gene expression in myotubes prepared from both healthy subjects and type 2 diabetic patients. In cells from control subjects, incubation with the agonist for 48 h affected neither insulin-induced rate of glycogen synthesis nor the phosphorylation state of protein kinase B (PKB serine 473). Myotubes from type 2 diabetic patients displayed marked reduction in the effects of insulin on glycogen synthesis and on PKB phosphorylation. However, treatment with PPARbeta agonists did not restore these defects. Therefore, these results indicate that induction of fatty acid oxidation with PPARbeta activators during short-term exposition is not sufficient to correct for insulin resistance in muscle cells from type 2 diabetic patients. This suggests that additional studies are needed to better characterize the link between fatty acid oxidation and insulin sensitivity in humans.

Cells, Cultured↗
PubMed2006

Waist circumference and the metabolic syndrome predict the development of elevated albuminuria in non-diabetic subjects: the DESIR Study.

OBJECTIVE: Metabolic determinants of microalbuminuria remain poorly understood in non-diabetic individuals and particularly in women. We investigated in both sexes whether an elevated waist circumference (WC) or the presence of the metabolic syndrome (MetS) predict the development of elevated albuminuria at 6 years. DESIGN AND PATIENTS: We studied 2738 subjects from the DESIR cohort without microalbuminuria or diabetes at baseline and who were followed up for 6 years. RESULTS: At 6 years, 254 individuals [9.3%; 95% confidence interval (CI) 8.2-10.4%] had developed elevated albuminuria (> or = 20 mg/l), which was significantly and positively associated with WC and blood pressure, but not with fasting glucose, lipids or body mass index in either sex. In both sexes, subjects with a high WC or with MetS at baseline were more likely to develop elevated albuminuria at 6 years compared with those with a normal WC or absence of MetS. In multivariate logistic analysis, WC as a continuous variable or a WC of 94 cm or greater for men and a WC greater than 88 cm for women were predictive of the development of elevated albuminuria, after adjusting for age, hypertension, the use of angiotensin-converting enzyme inhibitors, fibrinogen and glycaemia. MetS was a risk factor for elevated albuminuria in men (odds ratio 1.87; 95% CI 1.25-2.81), with differences according to the MetS definition. CONCLUSION: Abdominal adiposity is related to the development of elevated albuminuria in both sexes, suggesting that the measurement of WC may improve the identification of non-diabetic individuals at risk of developing microalbuminuria and emphasizing the interest of screening for albuminuria among those with MetS.

Adult↗
PubMed2006

Adiponutrin gene is regulated by insulin and glucose in human adipose tissue.

OBJECTIVE: Adiponutrin is a new transmembrane protein specifically expressed in adipose tissue. In obese subjects, short- or long-term calorie restriction diets were associated with a reduction in adiponutrin gene expression. Adiponut.rin mRNA level was previously shown to be negatively correlated with fasting glucose plasma levels and associated with insulin sensitivity of non-diabetic obese and non-obese subjects. The purpose of the present work was to get more insight into the regulation of adiponutrin gene expression by insulin and/or glucose using clamp studies and to examine its potential dysregulation in subjects with a deterioration of glucose homeostasis. METHODS: Adiponutrin gene expression was quantified by reverse transcriptase-quantitative PCR in s.c. adipose tissue of healthy lean subjects after an euglycemic hyperinsulinemic clamp (EGHI), a hyperglycemic euinsulinemic clamp, and a hyperglycemic hyperinsulinemic (HGHI) clamp. Adiponutrin gene expression was also analyzed in patients with different levels of insulin resistance. RESULTS: During EGHI, insulin infusion induced adiponutrin gene expression 8.4-fold (P = 0.008). Its expression was also induced by glucose infusion, although to a lesser extend (2.2-fold, P = 0.03). Infusion of both insulin and glucose (HGHI) had an additive effect on the adiponutrin expression (tenfold, P = 0.008). In a pathological context, adiponutrin gene was highly expressed in the adipose tissue of type-1 diabetic patients with chronic hyperglycemia compared with healthy subjects. Conversely, adiponutrin gene expression was significantly reduced in type-2 diabetics (P = 0.01), but remained moderately regulated in these patients after the EGHI clamp (2.5-fold increased). CONCLUSION: These results suggest a strong relationship between adiponutrin expression, insulin sensitivity, and glucose metabolism in human adipose tissue.

Adipose Tissue↗
PubMed2005

Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6.

The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)alpha or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFalpha or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFalpha and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.

Charcot-Marie-Tooth Disease↗
PubMed2005

[Editorial].

Explore the source record for details and available documents.

Editorial↗
PubMed2004

Effect of venous drainage site on insulin action after simultaneous pancreas-kidney transplantation.

BACKGROUND: The aim of the present study was to determine the influence of the venous drainage site on insulin homeostasis in simultaneous pancreas-kidney (SPK) transplant recipients. METHODS: The study included 12 SPK patients with portal venous drainage (P) and 11 SPK patients with systemic venous drainage (S) of pancreas allograft. All of the participants presented similar characteristics. The euglycemic hyperinsulinemic clamp was performed using a 0.4-mU/kg/min insulin infusion. An infusion of [6,6-(2)H2] glucose was used to determine glucose turnover at the basal state and during the clamp to determine liver and peripheral tissue sensitivity to insulin. RESULTS: Minor changes in glycemia and insulinemia were shown: fasting plasma glucose was significantly higher in the SPK-P group and insulinemia was higher in the SPK-S group. Hepatic glucose production was similar in both groups. During the clamp, insulin levels were higher in SPK-S recipients, but hepatic glucose production was suppressed in both groups. Glucose use was lower in SPK-S recipients than in SPK-P recipients, 3.32 +/-1.41 mg/kg/min and 4.70 +/-1.64 mg/kg/min, respectively (P<0.02). Basal and under-clamp free fatty acid levels were similar. In addition, no significant difference in cholesterol and low-density lipoprotein levels was shown, whereas high-density lipoprotein levels were higher in the SPK-S group; triglycerides during fasting and under clamp were significantly higher in the SPK-P group. CONCLUSIONS: In both groups, neither hepatic nor peripheral insulin resistance was detected. In SPK-S recipients, the authors have showed only a lower insulin clearance and a slight decreased peripheral responsiveness to insulin without modifications of lipid status.

Adult↗
PubMed2004

Increased adipose tissue expression of Grb14 in several models of insulin resistance.

Grb14 is an effector of insulin signaling, which directly inhibits insulin receptor catalytic activity in vitro. Here, we investigated whether the expression of Grb14 and its binding partner ZIP (PKC zeta interacting protein) is regulated during insulin resistance in type 2 diabetic rodents and humans. Grb14 expression was increased in adipose tissue of both ob/ob mice and Goto-Kakizaki (GK) rats, whereas there was no difference in liver. An increase was also observed in subcutaneous adipose tissue of type 2 diabetic subjects when compared with controls. ZIP expression was increased in adipose tissue of ob/ob mice and type 2 diabetic patients, but it did not vary in GK rats. Hormonal regulation of Grb14 and ZIP expression was then investigated in 3T3-F442A adipocytes. In this model, insulin stimulated Grb14 expression, while TNF-alpha increased ZIP expression. Moreover, the insulin-sensitizing drugs thiazolidinediones (TZDs) decreased Grb14 expression in 3T3-F442A adipocytes. Finally, we investigated the dynamic regulation of Grb14 expression in ob/ob mice in several conditions improving their insulin sensitivity. Prolonged fasting and treatment with metformin significantly decreased Grb14 expression in peri-epidydimal adipose tissue, while there was only a trend to a diminution after TZD treatment. Taken together, these results suggest that the regulation of Grb14 expression in adipose tissue may play a physiological role in insulin sensitivity.

3T3 Cells↗
PubMed2004

Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects.

Adipose tissue produces inflammation and immunity molecules suspected to be involved in obesity-related complications. The pattern of expression and the nutritional regulation of these molecules in humans are poorly understood. We analyzed the gene expression profiles of subcutaneous white adipose tissue from 29 obese subjects during very low calorie diet (VLCD) using cDNA microarray and reverse transcription quantitative PCR. The patterns of expression were compared with that of 17 non-obese subjects. We determined whether the regulated genes were expressed in adipocytes or stromavascular fraction cells. Gene expression profiling identified 100 inflammation-related transcripts that are regulated in obese individuals when eating a 28 day VLCD but not a 2 day VLCD. Cluster analysis showed that the pattern of gene expression in obese subjects after 28 day VLCD was closer to the profile of lean subjects than to the pattern of obese subjects before VLCD. Weight loss improves the inflammatory profile of obese subjects through a decrease of proinflammatory factors and an increase of anti-inflammatory molecules. The genes are expressed mostly in the stromavascular fraction of adipose tissue, which is shown to contain numerous macrophages. The beneficial effect of weight loss on obesity-related complications may be associated with the modification of the inflammatory profile in adipose tissue.

Adipose Tissue↗
PubMed2004

Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients.

Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans. IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes. SOCS-3 mRNA levels were significantly increased in the skeletal muscle of type 2 diabetic patients compared with control subjects and correlated with reduced insulin-stimulated glucose uptake. In contrast, SOCS-3 mRNA levels were reduced in muscle of obese nondiabetic subjects compared with type 2 diabetic patients, despite similar circulating concentrations of IL-6. Increased SOCS-3 mRNA levels in diabetes were not attributable to hyperglycemia, as type 1 diabetic patients had normal SOCS-3 mRNA expression in muscle. However, the combination of high glucose and IL-6 levels in type 2 diabetic patients may induce SOCS-3 expression, as has been seen in human muscle cells. In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat. Taken together, our results showed that SOCS-3 expression in human skeletal muscle in vivo is not related to insulin resistance in the presence of elevated IL-6 concentrations and suggest that cytokine action could differ in type 2 diabetic patients and nondiabetic obese subjects.

Adipose Tissue↗
PubMed2003

Microarray profiling of human skeletal muscle reveals that insulin regulates approximately 800 genes during a hyperinsulinemic clamp.

Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin.

Adult↗
PubMed2003

Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.

In many cells and specially in muscle, mitochondria form elongated filaments or a branched reticulum. We show that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced during myogenesis and contributes to the maintenance and operation of the mitochondrial network. Repression of Mfn2 caused morphological and functional fragmentation of the mitochondrial network into independent clusters. Concomitantly, repression of Mfn2 reduced glucose oxidation, mitochondrial membrane potential, cell respiration, and mitochondrial proton leak. We also show that the Mfn2-dependent mechanism of mitochondrial control is disturbed in obesity by reduced Mfn2 expression. In all, our data indicate that Mfn2 expression is crucial in mitochondrial metabolism through the maintenance of the mitochondrial network architecture, and reduced Mfn2 expression may explain some of the metabolic alterations associated with obesity.

Animals↗
PubMed2003

Splanchnic tissues play a crucial role in uremic glucose intolerance.

OBJECTIVE: Determine the mechanism of glucose intolerance in chronically uremic subjects. DESIGN: Comparison of doubly labeled oral glucose tolerance tests. SUBJECTS: Seven nondialyzed chronically uremic subjects (creatinine, 420 +/- 104 micromol/L) and 7 healthy subjects, matched for age and body mass index. INTERVENTION: Plasma glucose was labeled by an infusion of dideuterated glucose started 120 minutes before ingestion of 1 g/kg of naturally 13C-enriched corn starch glucose. Glucose levels and oxidation were monitored for 330 minutes after glucose ingestion. RESULTS: Uremic subjects had normal fasting plasma glucose levels and impaired glucose tolerance with high plasma insulin (P <.001 versus controls). Glucose tolerance was impaired because of an increased total rate of appearance of glucose (cumulated on 330 minutes: uremic, 1,231 +/- 42 mg/kg/330 min, controls, 1,031 +/- 64; P <.05). Peripheral glucose uptake was increased (P <.05) because of an increased nonoxidative disposal (P =.051). CONCLUSIONS: Although peripheral glucose uptake resisted the stimulatory effect of the high insulin levels, glucose tolerance was impaired through splanchnic metabolic disturbances: reduced splanchnic glucose uptake and increased endogenous glucose production. The respective contribution of these abnormalities remains to be determined.

Blood Glucose↗
PubMed2003

Mechanism of increased plasma glucose levels after oral glucose ingestion in normal-weight middle-aged subjects.

BACKGROUND/AIMS: To determine the decline in glucose tolerance in normal-weight middle-aged subjects, we performed a cross-sectional study using double-labelled oral glucose tolerance tests in 8 middle-aged (46.3 +/- 0.9 years) and in 8 young (23.6 +/- 0.5) subjects with similar normal body weight. METHODS: Plasma glucose was labelled by an infusion of dideuterated glucose started 120 min before ingestion of 1 g/kg of naturally (13)C-enriched corn starch glucose. Glucose levels, substrate oxidation (indirect calorimetry) and exogenous glucose oxidation ((13)C enrichment of expired CO(2)) were monitored for 330 min. RESULTS: In the middle-aged subjects, the appearance of exogenous glucose was reduced (723 +/- 52 mg/kg/330 min) compared to young subjects (864 +/- 38; p < 0.05), and systemic glucose production was normal. Plasma glucose levels were increased due to a reduced glucose disappearance rate (middle aged: 1,046 +/- 61 mg/kg/330 min vs. young 1,242 +/- 67; p < 0.05), concerning both oxidative and non-oxidative disposal. This reduction was no longer apparent when the results were normalized for fat-free mass. Insulin levels were similar in young and middle-aged subjects. CONCLUSION: In normal-weight middle-aged individuals, glucose intolerance is mainly due to the reduction in the mass of fat-free glucose-utilizing tissues. The higher plasma glucose levels enable normal glucose supply to peripheral tissues, and increase splanchnic glucose uptake.

Adult↗