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L Tappy

Publications and source records attributed to L Tappy.

At least 127 records · Page 7Linked to original sources
PubMed1993

Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans.

BACKGROUND: Physiological hyperinsulinemia in lean human subjects stimulates sympathetic nerve activity and blood flow in skeletal muscle, but the underlying mechanism is unknown. Potential mechanisms include central neural or peripheral actions of insulin. Glucocorticoids may potentially interfere with both such actions and thereby may attenuate sympathoexcitatory and vasodilatory effects of insulin in skeletal muscle. METHODS AND RESULTS: To determine whether insulin-induced sympathetic activation and vasodilation are attenuated by dexamethasone, we measured muscle sympathetic nerve activity and muscle blood flow during euglycemic hyperinsulinemia before and after short-term administration of this pharmacological agent. Insulin concentrations, which normally doubled sympathetic activity and markedly increased blood flow, had no such stimulatory effect after short-term dexamethasone administration. In contrast, responses to two noninsulin sympathetic stimuli, the Valsalva maneuver and immersion of the hand in ice water, and the vasodilatory response to calf vascular occlusion were not altered by dexamethasone. CONCLUSIONS: These results demonstrate a dramatic impairment of insulin-induced sympathetic activation and vasodilation by dexamethasone in lean, healthy humans. This study suggests that dexamethasone administration to lean subjects may offer an experimental model to examine underlying mechanisms that regulate the interplay between cardiovascular, sympathetic, and metabolic effects of insulin.

Adult↗
PubMed1993

Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans.

Euglycemic hyperinsulinemia evokes both sympathetic activation and vasodilation in skeletal muscle, but the mechanism remains unknown. To determine whether insulin per se or insulin-induced stimulation of carbohydrate metabolism is the main excitatory stimulus, we performed, in six healthy lean subjects, simultaneous microneurographic recordings of muscle sympathetic nerve activity, plethysmographic measurements of calf blood flow, and calorimetric determinations of carbohydrate oxidation rate. Measurements were made during 2 h of: (a) insulin/glucose infusion (hyperinsulinemic [6 pmol/kg per min] euglycemic clamp), (b) exogenous glucose infusion at a rate matched to that attained during protocol a, and (c) exogenous fructose infusion at the same rate as for glucose infusion in protocol b. For a comparable rise in carbohydrate oxidation, insulin/glucose infusion that resulted in twofold greater increases in plasma insulin concentrations than did glucose infusion alone, evoked twofold greater increases in both muscle sympathetic nerve activity and calf blood flow. Fructose infusion, which increased carbohydrate oxidation comparably, but had only a minor effect on insulinemia, did not stimulate either muscle sympathetic nerve activity or calf blood flow. These observations suggest that in humans hyperinsulinemia per se, rather than insulin-induced stimulation of carbohydrate metabolism, is the main mechanism that triggers both sympathetic activation and vasodilation in skeletal muscle.

Adult↗
PubMed1993

Plasma IGF-1 binding proteins in lean and obese non-diabetic subjects.

Obese patients have markedly increased plasma insulin concentrations indicating insulin resistance. In contrast, plasma IGF-1 concentrations are little affected. Since the biological effects of IGF-1, including several insulin-like actions, appear to be modulated by serum carrier proteins, alterations of IGF-1 binding proteins were investigated in the serum of lean healthy individuals, and of obese patients with normal glucose tolerance. Obese patients had increased fasting plasma insulin and decreased plasma h-GH concentrations, compared to lean controls. IGF-1 concentrations were similar in both groups. Serum IGF-1 binding proteins were separated by polyacrylamide gel electrophoresis under non-reducing conditions, electroblotted onto a nitrocellulose sheet, and quantified by ligand blot with 125I IGF-1 and autoradiography. IGF-1 binding proteins of apparent molecular weight 42 kDa, 39 kDa, 35 kDa, 30 kDa and 24 kDa were observed. Obese patients had a level of IGF-1 binding proteins of 35 kDa which was decreased to 40 +/- 25% (s.d.) of control values. This 35 kDa protein corresponds to IGF-BP2, which may be involved in glucose homeostasis. It is concluded that alterations of IGF-1 binding proteins are present in obesity and may have consequences for glucose metabolism.

Adult↗
PubMed1992

Thermogenesis and fructose metabolism in humans.

Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182 cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20% at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg, 1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further 2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1) euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2 muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than 0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P) and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1 (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6 mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and 12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was suppressed to varying degrees during the euglycemic clamp. It is concluded that 1) the greater thermic effect of fructose compared with glucose is probably due to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin) and the energy cost of fructose metabolism to glucose in the liver. 2) There is a sympathetically mediated component to the thermic effect of fructose (approximately 30%) that is not mediated by elevated plasma insulin concentrations similar to those observed with iv glucose.

Adrenergic beta-Antagonists↗
PubMed1992

Effects of infused amino acids on glucose production and utilization in healthy human subjects.

Amino acids have been reported to increase endogenous glucose production in normal human subjects during hyperinsulinemia: however, controversy exists as to whether insulin-mediated glucose disposal is inhibited under these conditions. The effect of an amino acid infusion on glucose oxidation rate has so far not been determined. Substrate oxidation rates, endogenous glucose production, and [13C]glucose synthesis from [13C]bicarbonate were measured in six normal human subjects during sequential infusions of exogenous glucose and exogenous glucose with (n = 5) or without (n = 5) exogenous amino acids. Amino acids increased endogenous glucose production by 84% and [13C]glucose synthesis by 235%. Glucose oxidation estimated from indirect calorimetry decreased slightly after amino acids, but glucose oxidation estimated from [13C]glucose-13CO2 data was increased by 14%. It is concluded that gluconeogenesis is the major pathway of amino acid degradation. During amino acid administration, indirect calorimetry underestimates the true rate of glucose oxidation, whereas glucose oxidation calculated from the 13C enrichment of expired CO2 during [U-13C]glucose infusion does not. A slight stimulation of glucose oxidation during amino acid infusion, concomitant with an increased plasma insulin concentration, indicates that amino acids do not inhibit glucose oxidation.

Adult↗
PubMed1992

Metabolic and respiratory effects of infused sodium acetate in healthy human subjects.

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.

Acetates↗
PubMed1991

Effects of muscarinic blockade on the thermic effect of oral or intravenous carbohydrate.

Muscarinic blockade by atropine has been shown to decrease the thermic effect of a mixed meal, but not of intravenous glucose. To further delineate the mechanisms involved in the atropine-induced inhibition of thermogenesis after a meal, plasma substrate and hormone concentrations, energy expenditure (EE) and substrate oxidation rates were measured before and during a continuous glucose infusion (44.4 mumol.kg-1.min-1) with or without atropine. After 2 h of glucose infusion, a 20-g oral fructose load was administered while the glucose infusion was continued. Plasma insulin concentrations attained a plateau at 596 (SEM 100) pmol.l-1 after 120 min of glucose infusion and were not affected by muscarinic blockade; plasma glucose concentrations peaked at 13.3 (SEM 0.5) mmol.l-1 at 90 min and decreased progressively thereafter; no difference was observed with or without atropine. Plasma free fatty acid and glucagon concentrations, with or without atropine, were both decreased to 201 (SEM 18) mumol.l-1 and 74 (SEM 4) ng.l-1, respectively, after 2 h of glucose infusion, and were not further suppressed after oral fructose. Carbohydrate oxidation rates (CHO(ox)) increased to 20.8 (SEM 1.4) mumol.kg-1.min-1 and lipid oxidation rates (Lox) decreased to 1.5 (SEM 0.3) mumol.kg-1.min-1 between 90 and 120 min after the beginning of glucose infusion and were not affected by atropine. Glucose-induced thermogenesis was similar with [6.5% (SEM 1.4%) of basal EE] or without [6.0% (SEM 1.0%), NS) muscarinic blockade during the 30 min preceding fructose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

A radioimmunoassay for human insulin receptor correlation between insulin binding and receptor mass.

We have developed a radioimmunoassay for human insulin receptor. Serum from a patient with Type B severe insulin resistance was used as anti-insulin receptor antiserum. Pure human placental insulin receptor was used as reference preparation and 125I labeled pure insulin receptor as trace. The radioimmunoassay was sensitive (limit of detection less than 17 fmol), reproducible (inter and intra-assay coefficients of variation 12.5% and 1.6% respectively) and specific (no crossreactivity with pure placental IGF-1 receptor, insulin and glucagon). The anti-insulin receptor antibody was, however, able to differentiate between insulin receptor from human placenta and from rat liver. To determine the number of insulin binding sites per receptor, we measured insulin binding (by insulin binding assay) and insulin receptor mass (by radioimmunoassay) in solubilized aliquots from 5 human placentas. The molar ratio of insulin binding to receptor mass was 0.86 +/- 0.12 when binding was determined with monoiodinated 125I-Tyr A 14-insulin. It was 1.94 +/- 0.27 when randomly iodinated 125I-insulin was used. In conclusion, using a sensitive, reproducible and specific radioimmunoassay, we have measured insulin receptor mass independent of insulin binding. Our data are most compatible with binding of one insulin molecule per human placental insulin receptor.

Autoantibodies↗
PubMed1991

Effects of muscarinic blockade on insulin secretion and on glucose-induced thermogenesis in lean and obese human subjects.

To determine whether hyperinsulinaemia of human obesity is dependent on the activity of the parasympathetic nervous system, and whether activation of the parasympathetic nervous system plays a role in glucose-induced thermogenesis, the metabolic effect of a continuous intravenous glucose infusion [44.4 mumol kg-1 body weight (bw) min-1] with or without atropine infusion was assessed in 11 obese patients and 10 lean controls. Compared with lean controls, obese patients had increased basal and glucose-stimulated plasma insulin and C-peptide concentrations and increased plasma glucose concentrations during glucose infusion. Glucose oxidation during i.v. glucose was lower in obese patients than in lean controls. Glucose-induced thermogenesis was similar in obese patients and in lean controls. Atropine infusion did not affect basal plasma glucose, insulin or free fatty acid concentrations nor glucose-stimulated plasma glucose, insulin, C-peptide, glucagon or free fatty acid concentrations in both groups of subjects. Glucose and lipid oxidation rates and glucose-induced thermogenesis were also unaffected by atropine administration. It is concluded that (1) glucose-stimulated hyperinsulinaemia in human obesity is not dependent on a hyperactivity of the parasympathetic nervous system, which indicates that human obesity is different from most animal models of obesity; (2) glucose-induced thermogenesis is similar in obese and lean subjects when a similar load of glucose is administered; (3) inhibition of the parasympathetic nervous system does not affect the thermic effect of i.v. glucose.

Adult↗
PubMed1991

Prevalence of diabetes and obesity in the adult population of the Seychelles.

The prevalence of diabetes and obesity were assessed in an age- and sex-stratified sample of 1078 individuals living in Mahé, The Republic of Seychelles. Presence or absence of diabetes mellitus was assessed by measuring glucose concentration in fasting venous blood. Prevalence of obesity (standardized for age) was elevated five-fold in women compared with men (20.9 vs 4.2%). In women, it increased from 8.9% at age 25-34 years to 29.4% at age 35-44 years and plateaued thereafter, whereas it did not change with age in men. Prevalence of diabetes (standardized for age) was 3.4% for men and 4.6% for women. It increased markedly with age, from 0.0 and 0.8% at age 25-34 years to 8.8 and 13.4% at age 55-64 years in men and women, respectively. A strong association of diabetes with excess body weight was observed. Most cases of diabetes can be attributed to Type 2 (non-insulin-dependent) diabetes. Fifty-five percent of diabetic individuals were unaware of their disease at the time of the survey.

Adult↗
PubMed1991

Energy and substrate metabolism in obesity and postobese state.

The total energy expenditure (EE) of human beings is represented by basal metabolic rate (which corresponds to 60-70% of EE), dietary-induced thermogenesis (10% of EE), and the energy expended in physical activity (20-30% of EE). Obese individuals have an increased total EE compared with lean subjects; this increase is essentially due to an increased lean body mass concomitant with obesity, and is completely reverted after weight loss. Glucose-induced thermogenesis (GIT), measured during an oral glucose tolerance test (OGTT) or hyperinsulinemic-euglycemic clamps, has been found to be decreased in obese individuals, although some discrepancy exists between studies. The observed decreases in GIT show a gradation, increasing progressively from obese patients with normal glucose tolerance to obese patients with impaired glucose tolerance (IGT) to obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and an increased insulin response after OGTT to obese patients with NIDDM and a hypoinsulinemic response after OGTT. The defect in GIT appears to be related to impairment in nonoxidative glucose storage and with the degree of insulin resistance. Obese patients after weight loss show a further decrease in GIT after OGTT or during a euglycemic clamp, which remains unclear. Obese patients have an increased basal lipid oxidation and a decreased suppression of lipid oxidation after OGTT or during a euglycemic clamp. Glucose oxidation and storage are both markedly decreased during a euglycemic clamp. In contrast, the defect in glucose storage is less apparent after OGTT, due to the compensatory effect of hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Relationship of fasting serum insulin concentrations with blood pressure in a representative sample of the adult population of the Seychelles.

Several studies have been performed to determine if plasma insulin concentration bears a relationship with blood pressure and may be a causative factor in the genesis of hypertension. The results reported were discrepant between studies: insulin was observed to be independently correlated with blood pressure in some studies, whereas no such relationship was observed in others. Serum insulin, whole blood glucose, weight, height, and diastolic and systolic blood pressure of 839 fasting individuals, randomly selected from the adult population of Mahé Island, The Seychelles, were recorded; this population has a high hypertension prevalence rate. The proportion of hypertension was higher in subgroups of individuals with diabetes mellitus (52.4 percent) and with overweight (34.5 percent) than in the general population. Subgroups of individuals with diabetes, excessive weight or high blood pressure had higher mean fasting plasma insulin (13.6 +/- (s.d.) 7.9, 14.0 +/- 8.0, 11.1 +/- 9.7 respectively) than individuals not affected with these conditions (8.1 +/- 4.6 microU/ml). Both systolic and diastolic blood pressure were positively correlated with age, body mass index and fasting blood glucose in a multivariate model. No correlation with insulin was observed. In contrast, in a subgroup of 223 overweight individuals, age, blood glucose and plasma insulin were each positively correlated with blood pressure. It is concluded that, in this cross-sectional study, insulin was not independently correlated with blood pressure except for overweight individuals.

Adult↗
PubMed1990

Resting metabolic rate and body composition of achondroplastic dwarfs.

Indirect calorimetry was used to measure resting metabolic rates (RMR), and densitometry and anthropometry were used to measure body fat and fat-free masses of 32 adults with very short stature. Twenty-seven of them were achondroplastic dwarfs. Their results were compared to those obtained from 103 lean and obese adults with normal heights. All 32 dwarfs had distinctly greater RMR per kg fat-free mass by densitometry than adults with average stature. However, there was a wide variation in the RMR among dwarfs, which was independent of leanness or obesity. In spite of increased RMR, obesity among dysplastic adult dwarfs was twice as prevalent as among average-height adults. Increased abdominal:hip ratios were prevalent among dwarfs, but these ratios do not reflect body fat. Body mass indices were worthless, and skinfold thicknesses and other anthropometric measurements were of very limited value in predicting the body fat of dwarfs. Although our new and specific equations for estimating RMR and body composition give reasonable values, we recommend that the caloric requirements and body compositional variables be measured if nutritional therapy is needed to induce weight loss or gain in Little People.

Achondroplasia↗
PubMed1990

Role of glucagon in disposal of an amino acid load.

Amino acids stimulate the release of glucagon and insulin. To assess the role of aminogenic hyperglucagonemia, we have studied, in healthy young males, the effects of basal (less than 100 pg/ml) and high (200-400 pg/ml) plasma glucagon concentrations on amino acid metabolism during intravenous infusion (0.5 g.h-1.4 h) of a mixture of 15 amino acids. Basal plasma glucagon concentrations were obtained by infusion of somatostatin (0.5 mg/h) plus glucagon (0.25 ng.kg-1.min-1) and high plasma glucagon concentrations by infusion of somatostatin plus glucagon (3.0 ng.kg-1.min-1) or by infusion of amino acids alone. All studies were performed under conditions of euglycemic (83-91 mg/dl) hyperinsulinemia (50-80 microU/ml). Hyperglucagonemia significantly increased 1) net amino acid transport from the extracellular into the intracellular space (by approximately 4%), 2) net degradation of amino acids entering the intracellular space (by approximately 40%), and 3) conversion of degraded amino acids into glucose from 0-10% (basal glucagon) to 70-100% (high glucagon). Hyperglucagonemia did not affect the amount of amino acids excreted in the urine (approximately 4%). We conclude that glucagon plays an important role in the disposition of amino acids by increasing their inward transport, their degradation, and their conversion into glucose.

Adult↗
PubMed1990

Effects of amino acids on glucose disposal.

Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This action may play an important role in the pathophysiology of insulin resistance and non-insulin-dependent diabetes mellitus. To investigate whether amino acids (AAs) have similar actions, we determined the effects of an intravenously infused mixture of 15 AAs on carbohydrate disposal during euglycemic-hyperinsulinemic clamps associated with either basal or high glucagon concentrations in healthy male volunteers. Plasma glucose concentration was clamped at approximately 4.7 mM (coefficient of variation 4.7%). Insulin infusion (7.18 pmol.kg-1.min-1) raised serum insulin concentrations from 36-50 pM to between 300 and 600 pM. AA infusions (0.5 g.kg-1.h-1.4 h) raised plasma alpha-amino N2 concentrations about five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory factor, SRIF), and high-glucagon replacement (3.0 ng.kg-1.min-1) reduced the rate of exogenous glucose infusion needed to maintain euglycemia from 51.1 +/- 7.2 mumol.kg-1.min-1 (saline + SRIF + high glucagon) to 28.3 +/- 11.1 mumol.kg-1.min-1 and stimulated endogenous glucose production (from 0 to approximately 17 mumol.kg-1.min-1). Thus, glucose disposal (exogenous infusion plus endogenous production of glucose) remained essentially unchanged. During infusion of AAs + SRIF + basal glucagon replacement (0.25 ng.kg-1.min-1), endogenous glucose production remained completely suppressed, and the rates of exogenous glucose infusion did not change (compared with saline + SRIF + basal glucagon replacement). The data showed that 1) hyperaminoacidemia associated with hyperglucagonemia stimulated endogenous glucose production despite hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no inhibitory effect on insulin-stimulated total-body glucose disposal.

Adult↗