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Biomedical subjects

L Tappy

Publications and source records attributed to L Tappy.

At least 91 records · Page 5Linked to original sources
PubMed1997

Measurement of substrate oxidation in man.

The measurement of substrate oxidation in living individuals can facilitate metabolic investigations. Indirect calorimetry and tracer techniques allow such measurements. Indirect calorimetry provides simultaneous calculation of the rate of oxidation of the three major macronutrients (carbohydrates, fat and protein) from respiratory gas exchanges and urinary nitrogen excretion. Such estimates represent net substrate oxidation rates. Thus, carbohydrate oxidation represents the oxidation of either endogenous glycogen or exogenously administered carbohydrate. It also includes de novo lipogenesis (with simultaneous oxidation of lipids in amounts equivalent to their synthesis), but does not include oxidation of glucose formed from gluconeogenesis from amino acids or glycerol. The accuracy of these calculations depends on the adequacy of the stoichiometry used for oxidation of substrates, which has to be varied when special forms of substrate are used. Tracer techniques consist in administration in tracer amounts of a selected nutrient labelled with 14C or 13C and monitoring of the specific activity/isotopic enrichment of the substrate in plasma and of the pulmonary elimination of labelled CO2. Such techniques allow assessment of the actual rate of oxidation of one substrate at a time. However, there are major pitfalls relating to the recovery of labelled CO2 in breath during oxidation of the substrate as well as during non-steady state conditions.

Calorimetry, Indirect↗
PubMed1996

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects.

Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g.kg fat free mass-1.h-1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7 +/- 1.9 mumol.kg fat free mass-1.min-1 basal vs 15.9 +/- 0.9 after fructose), in obese non-diabetic subjects (12.1 +/- 0.5 basal vs 13.1 +/- 0.5 after fructose) and in lean healthy subjects (13.3 +/- 0.5 basal vs 13.8 +/- 0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232 +/- 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p < 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i.e. glycogenolysis + gluconeogenesis from non-fructose precursors).

Administration, Oral↗
PubMed1996

Thermic effect of food and sympathetic nervous system activity in humans.

The intake of nutrients is known to increase energy expenditure. Measured thermic effects of nutrient are 0-3% for fat, 5-10% for carbohydrates and 20-30% for proteins. Stimulation of adenosine triphosphate (ATP) hydrolysis during intestinal absorption, initial metabolic steps and nutrient storage are responsible for this food thermic effect. The autonomic nervous system modulates the thermic effect of nutrients. Parasympathetic muscarinic antagonists reduce the thermic effect of orally administered nutrients, most likely by delaying gastric emptying and decreasing the amount of nutrient storage. Antagonists of the beta-adrenoreceptors decrease the thermic effect of glucose. The part of glucose induced thermogenesis which is eliminated by beta-adrenergic antagonists has been called 'facultative thermogenesis' and takes place, at least in part, in skeletal muscle. Insulin-induced stimulation of muscle sympathetic nerve activity may be involved in this facultative thermogenesis. The thermic effect of food is reduced in obese, insulin-resistant patients. The effect of thermogenesis represents about 50-150 kcal/day in such patients, and can explain only a minor part of their excess body weight. Defective thermogenesis may, however, contribute to weight gain, or impair weight loss in such patients.

Autonomic Nervous System↗
PubMed1996

Effects of sodium lactate on ventilation and acid-base balance in healthy humans.

Sodium lactate inhibits ventilation when infused in healthy human subjects. This effect has been attributed to lactate-induced metabolic alkalosis. In order to further delineate the mechanisms responsible for this depression of ventilation, healthy humans were infused with sodium lactate with or without acetazolamide. Sodium lactate increased blood pH from 7.37 +/- 0.02 to 7.47 +/- 0.01 and induced a sustained urinary excretion of bicarbonate. PO2 of arterialized blood decreased by 10.3 +/- 2.1 mmHg, indicating an inhibition of ventilation. Acetazolamide decreased lactate-induced alkalinisation of blood (pH after lactate + acetazolamide 7.42 +/- 0.02), but did not prevent the drop in PO2. Acetazolamide alone tended to stimulate ventilation, as indicated by an increase in PO2. These results indicate that sodium lactate inhibits ventilation independently of changes in systemic blood pH. Alkalinization of the cerebrospinal fluid, or other central effects of lactate, is probably responsible for this ventilatory depression.

Acetazolamide↗
PubMed1996

Effects of infused glucose on glycogen metabolism in healthy humans.

In order to determine whether or not hepatic glycogen breakdown contributes to systemic glucose flux during glucose infusion, net carbohydrate oxidation (indirect calorimetry) and the total rate of glucose appearance (6,6(-2)H-glucose) were measured in six healthy women during infusion of U-13 C labelled glucose (22 mumol/kg/min). Glucose infusion completely suppressed endogeneous glucose production and increased net carbohydrate oxidation from 10.9 +/- 1.6 to 18.9 +/- 1.0 mumol/kg/min. To differentiate between the oxidation of endogenous (i.e. glycogen) and of exogenous carbohydrates, the 13CO2 production was measured and the oxidation of exogenous 13C labelled carbohydrate was calculated. For this purpose, the specific recovery factor in breath of 13CO2 issued from oxidation of uniformly labelled glucose was determined during infusions of equimolar amounts of 13C bicarbonate, 1-13C acetate and 2-13C acetate. The average recovery was 53.9 +/- 1.5%. The oxidation of exogenous carbohydrate was 20.9 +/- 0.7 mumol/kg/min. This value was slightly higher than net carbohydrate oxidation, indicating that no oxidation of endogenous, unlabelled carbohydrate, and, hence, no utilization of hepatic glycogen took place. These results indicate that (i) estimation of glucose oxidation from indirect calorimetry and tracer technology give concordant results when an appropriate factor of 13CO2 recovery in breath is used, and (ii) utilization of previously formed glycogen is inhibited during hyperglycaemia and hyperinsulinaemia.

Adult↗
PubMed1996

Effects of hyperinsulinemia and hyperglycemia on lactate release and local blood flow in subcutaneous adipose tissue of healthy humans.

To determine the effects of hyperglycemia and hyperinsulinemia on lactate production by adipocytes, healthy volunteers were studied during three experimental protocols. In protocol 1, the changes in interstitial lactate concentrations were measured by microdialysis (sc tissue) after oral glucose administration. The plasma lactate concentration increased by 39.4 +/- 6.0%, and the dialysate lactate concentration increased by 117.9 +/- 16.3%. In protocol 2, a 2.5-h hyperinsulinemic euglycemic clamp and somatostatin infusion were performed. The plasma and dialysate lactate concentrations increased by 27.1 +/- 5.5% and 146.8 +/- 44.5%, respectively. In addition, [U-13C]glucose was infused through the probe, and dialysate lactate was enriched in 13C at 2.5 +/- 0.3 molar percent excess basally and at 3.4 +/- 0.3 molar percent excess during the clamp (P < 0.05 vs. basal). [13C]Urea was also infused through the probe, and the outflow to inflow ratio of [13C]urea was used as an index of local blood flow. It decreased by 10.2 +/- 3.6% (P < 0.001) at the end of the hyperinsulinemic euglycemic clamp, indicating an increase in blood flow. In protocol 3, a hyperglycemic clamp (10.0 mmol/L) at the basal insulin concentration was performed. It increased the dialysate lactate concentration by 43.5 +/- 15.9% and did not alter the plasma lactate concentration or local blood flow. It is concluded that hyperinsulinemia and, to a lesser extent, hyperglycemia stimulate glucose conversion into lactate in adipocytes. Hyperinsulinemia, but not hyperglycemia, also increases adipose tissue blood flow.

Adipose Tissue↗
PubMed1996

Effects of breakfast cereals containing various amounts of beta-glucan fibers on plasma glucose and insulin responses in NIDDM subjects.

OBJECTIVE: To determine whether increasing doses (amounts) of beta-glucan present in an extruded breakfast cereal affect the glycemic and insulinemic responses in eight NIDDM subjects, compared with the same responses after a continental breakfast (bread, milk, cheese, ham). RESEARCH DESIGN AND METHODS: Breakfast cereals were produced using various proportions of oat bran enriched in fiber, which contain an unusually high amount of a viscous polysaccharide, called beta-glucan, and oat bran. The carbohydrate load was 35 g. RESULTS: The maximum increases observed in plasma glucose after the breakfast cereal were 67% (P < 0.05), 42% (P < 0.001), and 38% (P < 0.001) with 4.0, 6.0, and 8.4 g beta-glucan, respectively, compared with the continental breakfast. There was a linear inverse relationship between dose of beta-glucan and plasma glucose peak or area under the glucose curve (R2 = 0.94, P < 0.05). Postprandial insulin increase was only 59-67% (P < 0.01) as high as the continental breakfast after all three levels of beta-glucan. CONCLUSIONS: The 50% decrease in glycemic response that was observed after the ingestion of 35 g carbohydrate is estimated to occur with approximately 5 g beta-glucan. This dose of beta-glucan can easily be attained without the loss of taste by incorporating oat bran concentrate in products.

Adult↗
PubMed1996

Influences of body weight, body composition, and substrate oxidation rate on resting postabsorptive glucose production and gluconeogenesis.

OBJECTIVE: To determine the influence of body weight, fat mass, and fat distribution on resting endogenous glucose production in healthy lean and overweight individuals. DESIGN: measurements were performed in the resting postabsorptive state in individuals receiving an unrestricted diet. SETTING: Institute of Physiology of Lausanne University. MEASUREMENTS: resting post absorptive glucose production, glycogenolysis and gluconeogenesis; resting energy expenditure and net substrate oxidation. RESULTS: Endogenous glucose production was positively correlated with body weight, lean body mass, energy expenditure and carbohydrate oxidation. Gluconeogenesis was positively correlated with net lipid oxidation and energy expenditure, and negatively correlated with net carbohydrate oxidation. No correlation with body fat or fat distribution was observed. CONCLUSIONS: Gluconeogenesis shows a large interindividual variability. Net lipid oxidation and not body fat appears to be a major determinant of gluconeogenesis.

Adult↗
PubMed1995

Suppression of alcohol-induced hypertension by dexamethasone.

BACKGROUND: Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS: To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS: The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS: Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events.

Action Potentials↗
PubMed1995

Assessment of glucose metabolism in humans with the simultaneous use of indirect calorimetry and tracer techniques.

Concomitant measurements of sytemic glucose delivery and carbohydrate oxidation are frequently performed in human investigations. Systemic glucose delivery (SGD) is usually determined using dilution of infused glucose tracers; net carbohydrate oxidation rate (net CHOOX) can be calculated from respiratory gas exchanges and urinary nitrogen excretion (indirect calorimetry); alternatively, glucose oxidation can be measured from labelled CO2 production during infusion of carbon-labelled glucose tracers. In this paper, the theory underlying the use of each of these techniques is briefly reviewed and qualitative differences are outlined. SGD represents the sum of hepatic glucogenolysis, gluconeogenesis from amino acids or glycerol, and, according to the glucose tracer used, glucose cycles (glucose-phosphate cycle, fructose-phosphate cycle, Cori and glucose-alanine cycles); systemic delivery of exogenous glucose after oral or i.v. glucose administration is also measured. Net CHOOX represents oxidation of glucose arising from hepatic or muscle glycogen or from exogenous glucose; it does not take into account oxidation of glucose formed from amino acids or glycerol, which is included in net protein or lipid oxidation. In contrast, isotopic determination of glucose oxidation corresponds to oxidation of glucose originating from hepatic glycogen breakdown, of exogenously administered glucose, and of glucose formed from amino acids and glycerol. Non-oxidative glucose disposal, calculated as SGD-net CHOOX, corresponds to the sum of gluconeogenesis from amino acids or glycerol (which are included in net protein and lipid oxidation), glucose cycles, and glycogen synthesis.

Blood Glucose↗
PubMed1995

Effects of glucocorticoids and sympathomimetic agents on basal and insulin-stimulated glucose metabolism.

The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocorticoids show several interactions with the sympatho-adrenal system which may contribute to this decrease in insulin sensitivity: they enhance the synthesis and actions of catecholamines, but abolish insulin-induced activation of muscle sympathetic nerve activity. The present study was performed in order to investigate the effects of the interactions between glucocorticoids and the sympatho-adrenal system on insulin sensitivity. Basal and insulin-stimulated glucose metabolism was measured in healthy human subjects during four 2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2 days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake, production and oxidation were calculated from plasma 13C glucose and exhaled 13CO2 during constant tracer infusion of U-13C glucose. Basal glucose production, utilization and oxidation were similar in all four studies. During hyperinsulinaemia, glucose uptake was reduced by 51.5% with treatment D, by 25.9% with treatment E, and by 49.6% with D+E. Glucose oxidation was reduced by 54.0% with treatment D, by 24.0% with treatment E, and by 57.2% with D+E. Hepatic glucose production was completely suppressed in all four studies. It is concluded that both dexamethasone and ephedrine decrease insulin-mediated glucose uptake and oxidation. Co-administration of ephedrine does not suppress the glucocorticoid-induced alterations of glucose metabolism. This indicates that glucocorticoid-induced insulin resistance is not related to the inhibition of muscle sympathetic nerve activity. These results suggest instead that glucocorticoids and sympathomimetic agents may impair glucose metabolism by common actions.

Adult↗
PubMed1995

Effects of lactate infusion on hepatic gluconeogenesis and glycogenolysis.

Endogenous glucose production rate (EGPR) remains constant when lactate is infused in healthy humans. A decrease of glycogenolysis or of gluconeogenesis from endogenous precursors or a stimulation of glycogen synthesis, may all be involved; This autoregulation does not depend on changes in glucoregulatory hormones. It may be speculated that alterations in basal sympathetic tone may be involved. To gain insights into the mechanisms responsible for autoregulation of EGPR, glycogenolysis and gluconeogenesis were measured, with a novel method (based on the prelabelling of endogenous glycogen with 13C glucose, and determination of hepatic 13C glycogen enrichment from breath 13CO2 and respiratory gas exchanges) in healthy humans infused with lactate or saline. These measurements were performed with or without beta-adrenergic receptor blockade (propranolol). Infusion of lactate increased energy expenditure, but did not increase EGPR; the relative contributions of gluconeogenesis and glycogenolysis to EGPR were also unaltered. This indicates that autoregulation is attained, at least in part, by inhibition of gluconeogenesis from endogenous precursors. beta-adrenergic receptor blockade alone (with propranolol) did not alter EGPR, glycogenolysis or gluconeogenesis. During infusion of lactate, propranolol decreased the thermic effect of lactate but EGPR remained constant. This indicates that alterations of beta-adrenergic activity is not required for autoregulation of EGPR.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients.

Hepatic glucose production is autoregulated during infusion of gluconeogenic precursors. In hyperglycemic patients with multiple trauma, hepatic glucose production and gluconeogenesis are increased, suggesting that autoregulation of hepatic glucose production may be defective. To better understand the mechanisms of autoregulation and its possible alterations in metabolic stress, lactate was coinfused with glucose in healthy volunteers and in hyperglycemic patients with multiple trauma or critical illness. In healthy volunteers, infusion of glucose alone nearly abolished endogenous glucose production. Lactate increased gluconeogenesis (as indicated by a decrease in net carbohydrate oxidation with no change in total [13C]carbohydrate oxidation) but did not increase endogenous glucose production. In patients with metabolic stress, endogenous glucose production was not suppressed by exogenous glucose, but lactate did not further increase hepatic glucose production. It is concluded that 1) in healthy humans, autoregulation of hepatic glucose production during infusion of lactate is still present when glycogenolysis is suppressed by exogenous glucose and 2) autoregulation of hepatic glucose production is not abolished in hyperglycemic patients with metabolic stress.

Adolescent↗
PubMed1995

Effect of physical exercise on glycogen turnover and net substrate utilization according to the nutritional state.

To determine the metabolic effects of a single bout of exercise performed after a meal or in the fasting state, nine healthy subjects were studied over two 8-h periods during which net substrate oxidation was monitored by indirect calorimetry. On one occasion, exercise was performed 90 min after ingestion of a meal labeled with [U-13C]glucose [protocol meal-exercise (M-E)]. On the second occasion, exercise was performed after an overnight fast and was followed 30 min later by ingestion of an identical meal [protocol exercise-meal (E-M)]. Energy balances were similar in both protocols, but carbohydrate balance was positive (42.2 +/- 5.1 g), and lipid balance was negative (-11.1 +/- 2.0) during E-M, whereas they were nearly even during M-E. Total glycogen synthesis was calculated as carbohydrate intake minus oxidation of exogenous 13C-labeled carbohydrate (calculated from 13CO2 production). Total glycogen synthesis was increased by 90% (from 47.6 +/- 3.8 to 90.7 +/- 5.4 g, P < 0.0001) during E-M vs. M-E. Endogenous glycogen breakdown was calculated as net carbohydrate oxidation minus oxidation of exogenous carbohydrate and was increased by 44% (from 35.8 +/- 5.6 to 51.7 +/- 6.6 g, P < 0.004) during E-M. It is concluded that exercise performed in the fasting state stimulates glycogen turnover and fat oxidation.

Adult↗
PubMed1995

Insulin-induced sympathetic activation and vasodilation in skeletal muscle. Effects of insulin resistance in lean subjects.

Insulin-induced stimulation of blood flow and sympathetic nerve activity in skeletal muscle tissue is impaired in obesity, but the underlying mechanism is unknown. To determine whether insulin resistance alters sympathetic and vasodilatory responses to euglycemic hyperinsulinemia, in eight healthy subjects we measured calf blood flow and muscle sympathetic nerve activity (MSNA) (n = 5) during insulin/glucose infusion (euglycemic hyperinsulinemic [6 pmol.kg-1.min-1] clamp) performed alone and performed during concomitant fat emulsion infusion, a maneuver designed to induce insulin resistance. The major new finding is that fat emulsion infusion, which attenuated insulin-induced stimulation of carbohydrate oxidation by 39 +/- 7% (P < 0.01), did not have any detectable effect on insulin-induced vasodilatory and sympathetic responses: at the end of the 2-h clamp, blood flow and MSNA had increased by 35 +/- 6% (P < 0.01) and 152 +/- 58% (P < 0.01), respectively, during insulin infusion alone and by 35 +/- 7% (P < 0.01) and 244 +/- 90% (P < 0.01), respectively, during insulin infusion superimposed on free fatty acid infusion. These observations in lean healthy subjects indicate that induction of resistance to the stimulatory effects of insulin on carbohydrate metabolism does not attenuate muscle blood flow and MSNA responses evoked by acute euglycemic hyperinsulinemia. These findings provide further evidence that hyperinsulinemia per se is the primary stimulus that triggers stimulation of muscle blood flow and MSNA during insulin/glucose infusion in humans and suggest that the impaired insulin-induced vasodilation in obese subjects is not related primarily to impaired stimulation of muscle carbohydrate metabolism.

Adult↗
PubMed1995

Metabolic effects of an increase of sympathetic activity in healthy humans.

OBJECTIVE: To determine the metabolic effects of catecholamines released at sympathetic nerves ending in the postabsorptive and postprandial states. DESIGN: Sympathetic activity was acutely increased by lower body negative pressure (LBNP; -15 mmHg) on two occasions in a group of eight healthy volunteers: (1) in the postabsorptive state; and (2) after glucose ingestion. MEASUREMENTS: Plasma norepinephrine concentrations were determined by HPLC and energy expenditure and substrate oxidation rates were assessed with indirect calorimetry. RESULTS: After glucose, LBNP increased plasma norepinephrine by 27% and lipid oxidation by 72% and decreased glucose oxidation by 14%. Energy expenditure was not altered. In the postabsorptive state, LBNP increased plasma norepinephrine by 34%, but had no significant effect on energy or substrate metabolism. CONCLUSIONS: In healthy humans, LBNP-induced activation of the sympathetic nervous system decreases glucose oxidation and increases lipid oxidation after oral glucose, but does not quantitatively affect energy expenditure.

Adult↗
PubMed1995

Regulation of hepatic glucose production in healthy subjects and patients with non-insulin-dependent diabetes mellitus.

The regulation of endogenous glucose production is central to the control of blood glucose concentrations. In non-insulin-dependent diabetes mellitus (NIDDM), increased endogenous glucose production contributes to fasting hyperglycaemia. Gluconeogenesis appears to be exaggerated in NIDDM, and it may be hypothesized that an enhanced release of gluconeogenic precursors is responsible for increased total glucose output. However, it would appear that substrate-induced stimulation of gluconeogenesis fails to increase total glucose production in healthy humans and NIDDM patients. This autoregulation of endogenous glucose production may be attained by inhibition of glycogenolysis and/or gluconeogenesis from endogenous substrate. It has also been observed that stimulation of intrahepatic disposal of neoformed glucose (mainly as glycogen synthesis) contributes to autoregulation. These observations support the concept that intrahepatic disposal of glucose-6-phosphate plays a major role in the control of endogenous glucose production.

Diabetes Mellitus, Type 2↗