Biomedical subjects

L Tappy

Publications and source records attributed to L Tappy.

At least 109 records · Page 6Linked to original sources

PubMed1995

Effects of infused sodium lactate on glucose and energy metabolism in healthy humans.

To assess the effects of lactate on glucose metabolism, sodium lactate (20 mumol.kg-1.min-1) was infused into healthy subjects in basal conditions and during application of a hyperinsulinaemic (6 pmol.kg-1.min-1) euglycaemic clamp. Glucose rate of appearance (GRa) and disappearance (GRd) were measured from plasma dilution of infused U- 13C glucose, and glucose oxidation (G(ox)) from breath 13CO2 and plasma 13C glucose. In basal conditions, lactate infusion did not alter G(ox) (8.8 +/- 0.9 vs 9.2 +/- 1.1 mumol.kg-1.min-1), while GRa slightly decreased from 15.2 +/- 0.8 basal to 13.9 +/- 0.9 mumol.kg-1.min-1 after lactate (p < 0.05). During a hyperinsulinaemic clamp, hepatic glucose production was completely suppressed with or without lactate. Lactate decreased G(ox) from 17.1 +/- 0.4 to 13.4 +/- 1.2 mumol.kg-1.min-1 (p < 0.05), whereas GRd was unchanged (39.7 +/- 3.6 vs 45.6 +/- 2.6 mumol.kg-1.min-1. It is concluded that infusion of lactate in basal conditions does not increase GRa or interfere with peripheral glucose oxidation, and that during hyperinsulinaemia lactate decreases glucose oxidation but does not alter hepatic or peripheral insulin sensitivity.

Analysis of Variance↗

PubMed1994

[Differential diagnosis of insulin- and noninsulin-dependent diabetes mellitus--are there therapeutic implications?].

Although insulin-dependent and non insulin-dependent diabetes mellitus have a different pathogenesis, they are often indistinguishable by clinical and laboratory parameters. Complications in connection with diabetic micro- and macroangiopathy (retino-, nephro- and polyneuropathy, cardiovascular risks) are similar in both types of diabetes. Treatment is based on clinical presentation and routine laboratory tests, its goal is normoglycemia. The criteria for use of insulin are the same for all variants of diabetes. Control of associated cardiovascular risk factors is decisive. Diabetes is a clinical syndrome.

Algorithms↗

PubMed1994

Noninvasive assessment of in vivo glycogen kinetics in humans: effect of increased physical activity on glycogen breakdown and synthesis.

In vivo glycogen kinetics was estimated with the simultaneous use of indirect calorimetry and tracer technology in healthy humans during 24-h periods with low or moderate physical activity (1 or 3 exercise sessions each day). Two 13C-carbohydrates meals were administered at 9.30 a.m. and 1.30 p.m., and one 12C-carbohydrates meal at 6.30 p.m. Net carbohydrate oxidation (net CHO ox) was measured over a 24 h period by indirect calorimetry and oxidation of 13C-labelled carbohydrates (13C CHO ox) was estimated from 13CO2 production. Glycogen breakdown, assessed for the period 8.15 a.m.-6.30 p.m. as the difference between net CHO ox and 13C CHO ox, was increased 1.6 times with three exercise sessions [123.3 (SEM 8.0) g] versus one session [77.9 (SEM 7.7) g, P < 0.0001]. Carbohydrate balances over 24 h were close to zero under both conditions, indicating that glycogen breakdown was matched by an equivalent glycogen synthesis. It was concluded that simultaneous use of indirect calorimetry and tracer technology may make possible the estimation of glycogen kinetics in humans. Moderate physical activity enhanced both glycogen breakdown and synthesis. This stimulation of glycogen metabolism may therefore play a role in the enhanced insulin sensitivity induced by physical exercise.

Adult↗

PubMed1994

A non-invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man.

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55% carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50% of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 +/- 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 +/- 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Adult↗

PubMed1994

Effects of glucose and amino acid infusion on glucose turnover in insulin-resistant obese and type II diabetic patients.

Glucose turnover was assessed from [6,6-2H]glucose and [U-13C]glucose dilution analysis in six lean nondiabetic subjects, six obese patients with normal glucose tolerance, and six obese patients with non-insulin-dependent diabetes mellitus (NIDDM) during sequential infusions of glucose (13.9 mumol/kg fat-free mass [FFM]/min) and glucose+amino acid (4.2 mg/kg FFM/min). Cori cycle activity was assessed from the difference between glucose turnover obtained from [6,6-2H]glucose and [U-13C]glucose. During infusion of glucose alone, total glucose turnover was increased by 70% in obese NIDDM patients. Amino acid infusion decreased glucose concentrations by 0.8, 0.5, and 1.8 mmol/L in controls, obese patients, and NIDDM patients, respectively. This decrease in glycemia occurred despite an increase in glucose turnover in lean and obese nondiabetic subjects, and was due to an increased metabolic clearance rate (MCR) of glucose. In NIDDM patients the MCR of glucose was unchanged, and the decrease in glycemia was explained by a diminution in hepatic glucose output. Glucose turnover obtained by [6.6-2H] dilution analysis exceeded significantly the values obtained by dilution analysis in obese subjects and obese NIDDM patients, but not in controls. This indicates an increased Cori cycle activity in these patients.

Adolescent↗

PubMed1994

Overnight glucose metabolism in obese non-insulin-dependent diabetic patients and in healthy lean individuals.

Increased fasting hepatic glucose production is present in NIDDM patients, and has been shown to be due to increased gluconeogenesis. In order to determine the contribution of the cycling between glucose and three-carbon compounds (Cori and glucose-alanine cycles) to the increased hepatic glucose production, glucose kinetics measured overnight in seven obese NIDDM patients and six lean healthy subjects with both 6.6 2H glucose and U-13C glucose were determined. At 0500 h obese NIDDM subjects showed a 40% increase in glucose appearance calculated from 6.6 2H glucose, whereas glucose appearance calculated from U-13C glucose was similar compared to lean subjects, indicating increased glucose cycling. Non-oxidative glucose disposal was also increased three-fold in NIDDM patients. Glucose cycling was increased by 111% in NIDDM patients (118 +/- 18 mumole min-1 vs. 56 +/- 11 in controls, P < 0.05) and was positively correlated with plasma glucose concentration (r = 0.831, P < 0.001) and with non-oxidative glucose disposal (r = 0.714, P < 0.01). Four NIDDM patients were studied again after 3 days of insulin therapy. Insulin restored near-normoglycaemia (7.4 +/- 0.8 mmole l-1) and normalized rates of glucose appearance and glucose cycling. It is concluded that increased glucose cycling in obese NIDDM patients accounts for a major part of the increased fasting hepatic glucose production and non-oxidative glucose disposal in obese NIDDM subjects.

Adult↗

PubMed1994

Effects of infused fructose on endogenous glucose production, gluconeogenesis, and glycogen metabolism.

To determine the mechanisms that prevent an increase in gluconeogenesis from increasing hepatic glucose output, six healthy women were infused with [1-13C]fructose (22 mumol.kg-1.min-1), somatostatin, insulin, and glucagon. In control experiment, non-13C-enriched fructose was infused at the same rate without somatostatin, and [U-13C]glucose was infused to measure specifically plasma glucose oxidation. Endogenous glucose production (EGP, [6,6-2H]glucose), net carbohydrate oxidation (CHOox, indirect calorimetry), and fructose oxidation (13CO2) were measured. EGP rate did not increase after fructose infusion with (13.1 +/- 1.2 vs. 12.9 +/- 0.3 mumol.kg-1.min-1) and without (10.3 +/- 0.5 vs. 9.7 +/- 0.5 mumol.kg-1.min-1) somatostatin, despite the fact that gluconeogenesis increased. Nonoxidative fructose disposal, corresponding mainly to glycogen synthesis, was threefold net glycogen deposition, the latter calculated as fructose infusion minus CHOox (14.8 +/- 1.1 and 4.3 +/- 2.0 mumol.kg-1.min-1). It is concluded that 1) the mechanism by which EGP remains constant when gluconeogenesis from fructose increases is independent of changes in insulin and 2) simultaneous breakdown and synthesis of glycogen occurred during fructose infusion.

Adult↗

PubMed1994

Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans.

Euglycemic hyperinsulinemia stimulates both sympathetic nerve activity and blood flow to skeletal muscle, but the mechanism is unknown. Possible mechanisms that may stimulate muscle blood flow include neural, humoral, or metabolic effects of insulin. To determine whether such insulin-induced vasodilation is modulated by stimulation of adrenergic or cholinergic mechanisms, we obtained, in eight healthy lean subjects, plethysmographic measurements of calf blood flow during 3 h of hyperinsulinemic (1 mU.kg-1.min-1) euglycemic clamp performed alone or during concomitant beta-adrenergic (propranolol infusion), cholinergic (atropine infusion), or alpha-adrenergic (prazosin administration) blockade. Euglycemic hyperinsulinemia alone increased calf blood flow by 38 +/- 10% (means +/- SE) and decreased vascular resistance by 27 +/- 4% (P < 0.01). The principal new observation is that these insulin-induced vasodilatory responses were not attenuated by concomitant propranolol or atropine infusion, nor were they potentiated by prazosin administration. In conclusion, these findings provide evidence that during euglycemic hyperinsulinemia in lean healthy humans stimulation of muscle blood flow is not mediated primarily by beta-adrenergic or cholinergic mechanisms. Furthermore, alpha-adrenergic mechanisms do not markedly limit insulin-induced stimulation of muscle blood flow.

Adult↗

PubMed1994

Body fat and sympathetic nerve activity in healthy subjects.

BACKGROUND: Obesity is associated with an increased incidence of cardiovascular complications, but the underlying mechanism is unknown. In experimental animals, overfeeding is associated with sympathetic activation, and there is evidence that adrenergic mechanisms contribute to cardiovascular complications. METHODS AND RESULTS: We recorded resting postganglionic sympathetic nerve discharge (using intraneural microelectrodes) to skeletal muscle blood vessels in 37 healthy subjects covering a broad spectrum of percent body fat. To assess potential functional consequences of sympathetic nerve discharge, we simultaneously measured calf vascular resistance and energy expenditure. The resting rate of sympathetic nerve discharge to skeletal muscle was directly correlated with body mass index (r = .67, P < .0001) and percent body fat (r = .64, P < .0001). In addition to body fat, muscle sympathetic nerve activity was correlated with age (r = .40, P < .02), plasma insulin concentration (r = .34, P < .04), and plasma lactate concentration (r = .35, P < .04). Together, these four covariates accounted for 58% of the variance of muscle sympathetic nerve activity (P < .0001). The rate of sympathetic nerve discharge to calf blood vessels was directly correlated with calf vascular resistance (r = .40, P < .02) but did not predict energy expenditure (r = .22, P = .19). CONCLUSIONS: In healthy humans, body fat is a major determinant of the resting rate of muscle sympathetic nerve discharge. Overweight-associated sympathetic activation could represent one potential mechanism contributing to the increased incidence of cardiovascular complications in overweight subjects.

Adolescent↗

PubMed1994

Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans.

The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin-sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue.

Adult↗

PubMed1994

Mechanisms of dexamethasone-induced insulin resistance in healthy humans.

Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.

Adult↗

PubMed1994

Insulin resistance, hyperglycemia, and glucosuria in intensively milk-fed calves.

In intensively milk-fed calves post-prandial glucose (G) and insulin (I) concentrations, but not preprandial G concentrations, increased or failed to decrease during the growth period, compared with data from calves that were progressively weaned. This study was, therefore, designed to investigate G and I metabolism in veal calves. Euglycemic-hyperinsulinemic and hyperglycemic clamps in the unfed state demonstrated mutual responsiveness of I and G, but revealed a relative I resistance. After feed consumption, I resistance was exaggerated, as seen by decreased G clearance rates after i.v. G and I administration in fed compared with unfed calves. Milk replacer is a source of readily available lactose, fat, and protein, the intake of which, on a kilogram.75 basis, gradually increased with age. Increased substrate availability and effects of nutrients themselves were probably responsible for elevated plasma concentrations of G and I and led to I resistance. Additionally, hyperglycemia > 1.5 g/L was followed by urinary excretion of G.

Animal Feed↗

PubMed1994

Measurement of 13CO2 in expired air as an index of compliance to a high carbohydrate diet naturally enriched in 13C.

The aim of this study was to determine whether breath 13CO2 measurements could be used to assess the compliance to a diet containing carbohydrates naturally enriched in 13C. The study was divided into two periods: Period 1 (baseline of 4 days) with low 13C/12C ratio carbohydrates. Period 2 (5 days) isocaloric diet with a high 13C/12C ratio (corn, cane sugar, pineapple, millet) carbohydrates. Measurements were made of respiratory gas exchange by indirect calorimetry, urinary nitrogen excretion and breath 13CO2 every morning in post-absorptive conditions, both in resting state and during a 45-min low intensity exercise (walking on a treadmill). The subjects were 10 healthy lean women (BMI 20.4 +/- 1.7 kg/m2, % body fat 24.4 +/- 1.3%), the 13C enrichment of oxidized carbohydrate and breath 13CO2 were compared to the enrichment of exogenous dietary carbohydrates. At rest the enrichment of oxidized carbohydrate increased significantly after one day of 13C carbohydrate enriched diet and reached a steady value (103 +/- 16%) similar to the enrichment of exogenous carbohydrates. During exercise, the 13C enrichment of oxidized carbohydrate remained significantly lower (68 +/- 17%) than that of dietary carbohydrates. The compliance to a diet with a high content of carbohydrates naturally enriched in 13C may be assessed from the measurement of breath 13CO2 enrichment combined with respiratory gas exchange in resting, postabsorptive conditions.

Adult↗

PubMed1994

Effects of infused amino acids and lipids on glucose metabolism in healthy lean humans.

The effects of infusion of a triglyceride emulsion (which induces peripheral insulin resistance) and amino acids (which stimulate gluconeogenesis) on glucose metabolism were investigated in healthy lean humans during exogenous infusion of glucose. One group of subjects (n = 5) was infused for 7.5 h with 11.1 mumol/kg/min glucose; during the last 4 h, amino acids were also infused at a rate of 3.33 mg/kg/min. A second group of subjects (n = 5) was infused with glucose+lipids (Lipovenös, 10% 10 ml/min) for 7.5 h and amino acids were added during the last 4 h. Infusion of lipids suppressed the increase in glucose oxidation observed during infusion of glucose alone (delta glucose oxidation: -2.1 +/- 1.1 vs. + 4.5 +/- 1.4 mumol/kg/min; P < 0.05) and during infusion of glucose+amino acids (delta glucose oxidation: + 1.6 +/- 1.4 vs. + 10.6 +/- 1.2 mumol/kg/min; P < 0.05). Gluconeogenesis (determined from 13C glucose synthesis during infusion of 13C bicarbonate) increased from 1.1 +/- 0.2 mumol/kg/min during infusion of glucose and 1.6 +/- 0.3 during infusion of glucose+lipids to 3.2 +/- 0.4 and 3.1 +/- 0.4, respectively, when amino acid infusion was superimposed (P < 0.05 in both instances). Plasma glucose concentrations were identical during infusion of glucose alone or glucose+amino acids, with or without lipids. Insulin concentrations were significantly increased by lipids both during infusion of glucose alone and of glucose+amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Thermic effect of infused amino acids in healthy humans and in subjects with insulin resistance.

The thermic effect of food has been observed to be decreased in subgroups of obese nondiabetic and obese diabetic subjects. The mechanisms responsible for this decrease have not been fully elucidated. Although protein elicits the largest thermic effect among the various nutrients, most studies have addressed carbohydrate- or fat-induced thermogenesis in insulin resistance. To determine whether the decreased thermic effect of nutrients in insulin-resistant patients could be related to a decrease in protein-induced thermogenesis, glucose [13.9 mumol.kg fat-free mass (FFM)-1.min-1] with or without amino acids (4.2 mg.kg FFM-1.min-1) was infused into a group of six obese nondiabetic subjects (Ob), six obese subjects with non-insulin-dependent diabetes mellitus (NIDDM), and six lean subjects. The thermic effect of infused amino acid (% of infused energy) measured by indirect calorimetry was 21.1 +/- 3.2%, 23.8 +/- 1.8%, and 20.0 +/- 2.9% in lean, Ob, and NIDDM subjects, respectively (NS). It is concluded that the thermic effect of protein is not altered in insulin-resistant patients.

Adult↗

PubMed1993

Effects of infused sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate on energy expenditure and substrate oxidation rates in lean humans.

Infusion of sodium acetate in lean humans results in a decrease in respiratory exchange ratio, which may be advantageous in patients with respiratory failure. However, this potential decrease in respiratory work was observed to be offset by significant thermogenesis. The metabolic effects of sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate, infused at a rate of 20 mumol.kg-1.min-1 for 3 h, was monitored in six healthy human volunteers. Respiratory exchange ratio decreased from 0.85 +/- 0.02 at baseline to 0.75 +/- 0.02, 0.75 +/- 0.02, and 0.80 +/- 0.02, after acetate, lactate, or beta-hydroxybutyrate, respectively (P < 0.05 for each). Acetate produced a larger thermic effect (22.7% of energy infused) than did lactate (16.3%) or beta-hydroxybutyrate (13.6%). Thus, sodium salts of organic acids may potentially decrease the respiratory requirements by decreasing the respiratory exchange ratio. However, this effect is partially offset by the thermic effect of these substrates. The maximal doses and safety of these anions during larger infusion periods remain to be determined.

3-Hydroxybutyric Acid↗

PubMed1993

Fructose and dietary thermogenesis.

Ingestion of nutrients increases energy expenditure above basal metabolic rate. Thermogenesis of carbohydrate comprises two distinct components: an obligatory component, which corresponds to the energy cost of carbohydrate absorption, processing, and storage; and a facultative component, which appears to be related with a carbohydrate-induced stimulation of the sympathetic nervous system, and can be inhibited by beta-adrenergic antagonists. Fructose ingestion induces a greater thermogenesis than does glucose. This can be explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in obligatory thermogenesis. Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. These individuals in contrast display a normal thermogenesis after ingestion of fructose. This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin. This observation indicates that insulin resistance is likely to play an important role in the decreased glucose-induced thermogenesis of these individuals.

Body Temperature Regulation↗

PubMed1993

Enhanced insulin-dependent glucose utilization in iron-deficient veal calves.

Based on studies in Fe-deficient calves demonstrating enhanced blood lactate concentrations during treadmill exercise, the hypothesis was advanced that glucose metabolism is also disturbed at rest. Insulin-dependent glucose metabolism was therefore investigated in calves fed milk replacer containing 20 or 50 mg Fe/kg. Calves receiving only 20 mg Fe/kg of milk replacer developed moderate Fe deficiency anemia and had lower average daily gain than calves fed milk replacer containing 50 mg Fe/kg, but feed intake and feed refusals did not differ between groups. In Fe-deficient calves, insulin responses to glucose, based on intravenous and oral glucose tolerance and hyperglycemic clamp tests, were normal. Using hyperglycemic and euglycemic hyperinsulinemic clamps combined with [13C6]glucose infusions, glucose utilization and tissue sensitivity to insulin were greater in Fe-deficient calves than in Fe-adequate calves. Observed reductions in growth performance may be explained by decreased activity of Fe-dependent enzymes, increased anaerobic glycolysis and lactate-glucose cycling, adaptations that are expected to be energy expensive.

Animals↗