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Biomedical subjects

E Jequier

Publications and source records attributed to E Jequier.

At least 55 records · Page 3Linked to original sources

Effect of beta and alpha adrenergic blockade on glucose-induced thermogenesis in man.

After intravenous glucose/insulin infusion there is an increase in oxygen consumption and energy expenditure that has been referred to as thermogenesis. To examine the contribution of the beta and alpha adrenergic nervous system to this thermogenic response, 12 healthy volunteers participated in three studies: (a) euglycemic insulin (plasma insulin approximately 100 microunits/ml) clamp study (n = 12); (b) insulin clamp study after beta adrenergic blockade with intravenous propranolol for 1 h (n = 12); (c) insulin clamp study after alpha adrenergic blockade with phentolamine for 1 h (n = 5). During the control insulin clamp study total glucose uptake, glucose oxidation and nonoxidative glucose uptake averaged 7.85 +/- 0.47, 2.62 +/- 0.22, and 5.23 +/- 0.51 mg/kg X min. After propranolol infusion, insulin-mediated glucose uptake was significantly reduced, 6.89 +/- 0.41 (P less than 0.02). This decrease was primarily the result of a decrease in glucose oxidation (1.97 +/- 0.19 mg/kg X min, P less than 0.01) without any change in nonoxidative glucose metabolism. Phentolamine administration had no effect on total glucose uptake, glucose oxidation, or nonoxidative glucose disposal. The increments in energy expenditure (0.10 +/- 0.01 vs. 0.03 +/- 0.01 kcal/min) and glucose/insulin-induced thermogenesis (4.9 +/- 0.5 vs. 1.5 +/- 0.5%) were reduced by 70% during the propranolol/insulin clamp study. The increments in energy expenditure (0.12 +/- 0.03 kcal/min) and thermogenesis (5.0 +/- 1.5%) were not affected by phentolamine. These results indicate that activation of the beta adrenergic receptor plays an important role in the insulin/glucose-mediated increase in energy expenditure and thermogenesis. In contrast, the alpha adrenergic receptor does not appear to participate in this response.

Adult↗

A long-term study of different types of experimental alkaline reflux and the effects of its suppression in dogs.

The gastric mucosa of 19 mongrel dogs was submitted to a bilio-pancreatic, isolated biliary or isolated pancreatic reflux. With an isolated biliary reflux, there is a more rapid and more severe hyperaemia and foveolar hyperplasia of the mucosa of the fundus than with an isolated pancreatic reflux. There was no significant change in the basal serum level of gastrin with any of these different types of alkaline reflux, but we observed a statistically significant increase in the level of histamine in the gastric mucosa. Hyperaemia and foveolar hyperplasia of the fundic mucosa both disappeared when the alkaline reflux was suppressed, and there was a statistically significant decrease in the basal serum level of gastrin and in the level of histamine in the gastric mucosa.

Animals↗

Thermogenic responses induced by nutrients in man: their importance in energy balance regulation.

The regulation of body weight depends upon the control of food intake and the regulation of energy expenditure. In man, the control system for food intake may be overwhelmed by psychological or social influences and the thermogenic response to a variable energy input may play an important role in the energy regulatory system. Energy expenditure can be divided into 3 components: basal metabolic rate, thermogenesis and physical activity. Of these 3 components, thermogenesis, (i.e. the energy expended above the metabolic rate in the resting state) is the expenditure. The two main factors which contribute to thermogenesis, i.e food intake and cold exposure, elicit diet-induced thermogenesis (DIT) and non-shivering thermogenesis (NST), respectively. It is of interest to study thermogenesis in individuals who present a tendency to gain weight, in order to assess whether the thermogenic responses may be lower in these subjects than in lean controls. It has recently been shown that DIT consists of two separate components which can be described as "obligatory" and "regulatory" thermogenesis. The former is due to the energy costs of digesting, absorbing and converting the nutrients to their respective storage forms. The latter is an energy dissipative mechanism, mainly studied in animals. There is good experimental evidence showing that brown adipose tissue (BAT) is involved in the adaptive thermogenesis observed in rats fed a varied and palatable "cafeteria" diet. In addition, a thermogenic defect in BAT has been demonstrated in adult as well as young genetically obese animals, and this defect is present not only in adult, but also in young (12 day old) ob/ob mice, i.e. before the development of obesity. Thus, a defective thermogenesis seems to be a cause, rather than a consequence, of obesity in these animals. In man, the role of thermogenesis in energy balance regulation is not yet understood. Some conflicting results may have arisen from inadequate techniques to measure energy expenditure. In our laboratory, we have developed three different techniques to measure energy expenditure in man, namely direct calorimetry, indirect calorimetry using an open-circuit ventilated hood system, and a respiratory chamber. Data from recent studies on DIT in man support the concept that a defect in thermogenesis may contribute to energy imbalance and weight gain in obese individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Energy expenditure and whole body protein synthesis in very low birth weight (VLBW) infants.

To examine the rates of whole body protein synthesis and energy expenditure during the rapid growing period, premature infants of very low birth weight (VLBW) (less than 1500 g), appropriate for gestational age were kept under standard thermoneutrality conditions and received a formula diet providing 110 kcal/kg.d metabolisable energy (ME) and 3.3 g protein/kg.d. Their energy expenditure was measured by open circuit indirect calorimetry. Nitrogen turnover and whole body protein synthesis and catabolism were determined using repeated oral administration of 15N-glycine for 60-72 h followed by the analysis of 15N-enrichment in urinary urea. These VLBW infants grew at an average rate of 15 g/kg.d. About half of the ME intake (i.e. 50 kcal/kg.d) was invested in weight gain while the remainder (i.e. 60 kcal/kg.d) was oxidised. The energy equivalent of the weight gain (i.e. the amount of energy stored per g weight gain) and the N balance indicated that lean tissue made up approximately 2/3 of the weight gained and fat tissue the remaining 1/3. The plateau value for 15N enrichment reached on the third day of administration allowed us to calculate a rate of protein synthesis of 14 g/kg.d and protein breakdown of 12 g/kg.d in five VLBW fed a formula diet. The elevated energy expenditure of the very low birth weight infant seems to be related to its rapid rate of weight gain which is accompanied by a high rate of body protein synthesis. More than 20% of the total energy expenditure of the VLBW infants was accounted for by whole body protein synthesis.

Energy Metabolism↗

Energy cost of glucose storage in human subjects during glucose-insulin infusions.

The effect of graded levels of hyperinsulinemia on energy expenditure, while euglycemia was maintained by glucose infusion, was examined in 22 healthy young male volunteers by using the euglycemic insulin clamp technique in combination with indirect calorimetry. Insulin was infused at five rates to achieve steady-state hyperinsulinemic plateaus of 62 +/- 4, 103 +/- 5, 170 +/- 10, 423 +/- 16, and 1,132 +/- 47 microU/ml. Total body glucose uptake during each of the five insulin clamp studies was 0.41, 0.50, 0.66, 0.74, and 0.77 g/min, respectively. Glucose storage (calculated from the difference between total body glucose uptake minus total glucose oxidation) was 0.25, 0.29, 0.43, 0.49, and 0.52 g/min for each group, respectively, and represented over 60-70% of total glucose uptake. The net increment in energy expenditure after intravenous glucose was 0.08, 0.10, 0.14, 0.17, and 0.23 kcal/min, respectively. Throughout the physiological and supraphysiological range of insulinemia, there was a significant relationship (r = 0.95, P less than 0.001) between the increment in energy expenditure and glucose storage, indicating an energy cost of 0.45 kcal/g glucose stored. However, at each level of hyperinsulinemia, the theoretical value for the energy cost of glucose storage (assuming that all of the glucose is stored in the form of glycogen) could account for only 45-63% of the actual increase in energy expenditure that was measured by indirect calorimetry. These results indicate that factors in addition to glucose storage as glycogen must be responsible for the increase in energy expenditure that accompanies glucose infusion.

Adult↗

Metabolic effects of a mixed and a high-carbohydrate low-fat diet in man, measured over 24 h in a respiration chamber.

1. The relation between dietary carbohydrate: lipid ratio and the fuel mixture oxidized during 24 h was investigated in eleven healthy volunteers (six females, and five males) in a respiration chamber. Values of the fuel mixture oxidized were estimated by continuous indirect calorimetry and urinary nitrogen measurements. 2. The subjects, were first given a mixed diet for 7 d and spent the last 24 h of the 7 d period in a respiration chamber for continuous gas-exchange measurement. The fuels oxidized during 2.5 h or moderate exercise were also measured in the respiration chamber. After an interval of 2 weeks from the end of the mixed-diet period, the same subjects were given an isoenergetic high-carbohydrate low-fat diet for 7 d, and the same experimental regimen was repeated. 3. Dietary composition markedly influenced the fuel mixture oxidized during 24 h and this effect was still present 12 h after the last meal in the postabsorptive state. However, the diets had no influence on the substrates oxidized above resting levels during exercise. With both diets, the 24 h energy balance was slightly negative and the energy deficit was covered by lipid oxidation. 4. With the high-carbohydrate low-fat diet, the energy expenditure during sleep was found to be higher than that with the mixed diet. 5. It is concluded that: (a) the composition of the diet did not influence the fuel mixture utilized for moderate exercise, (b) the energy deficit calculated for a 24 h period was compensated by lipid oxidation irrespective of the carbohydrate content of the diet, (c) energy expenditure during sleep was found to be higher with the high-carbohydrate low-fat diet than with the mixed diet.

Adult↗

Energy expended during oxygen deficit period of submaximal exercise in man.

Aerobic (MR) and anaerobic (Man) metabolism was determined during the transition from mild (50 W external work) to heavier exercise (50% VO2max) in six subjects. The overall exercise efficiency was calculated during the oxygen deficit period and during steady-state exercise. MR was obtained by indirect calorimetry and Man by solving the heat balance equation: MR + Man - S = (R + C + E) + W, where radiative, convective, and evaporative heat losses (R + C + E) were measured by direct calorimetry, work output (W) by ergometry, and heat storage (S) by thermometry. (MR + Man) during the oxygen deficit period was found to be lower than MR during steady state. In the 1st min of exercise, mean mixed work efficiency (aerobic + anaerobic) was 33%, which was greater than aerobic efficiency (26.6%) during steady state. The mean anaerobic efficiency efficiency was 41%. This difference reflects the fact that the energy released by splitting of preformed high-energy bonds (i.e., creatine phosphate) is less than the energy released when high-energy bonds expended during mechanical work are continuously regenerated through oxidative phosphorylation. The reported measurements of overall energy metabolism in man provide means for estimating in vivo the coupling efficiency of physical work (i.e., 41%) as well as the efficiency with which energy released by substrate oxidations is recovered in the form of high-energy bonds (i.e., phosphorylation efficiency = 64%).

Aerobiosis↗

Energy expenditure during oxygen deficit of submaximal concentric and eccentric exercise.

Aerobic (MR) and anaerobic (Man) energy production was determined in five subjects during the 1st min of concentric and eccentric exercise (steady-state energy expenditure approximately 415 W in both situations). Man was obtained by solving the heat balance equation, MR + Man - S = (R + C + E) +/- parallel to W parallel to, all other variables of which could be measured [S is heat storage; (R + C + E) are the radiative, convective, and evaporative heat losses; and W is work output]. The size of the O2 deficit was similar whatever the type of exercise (99 +/- 19 W concentric and 102 +/- 19 W eccentric). MR + Man was lower than the steady-state MR in both types of exercise (concentric; 364 +/- 19 and 407 +/- 24 W, respectively, and eccentric; 346 +/- 25 and 430 +/- 21 W, respectively). The size of the O2 deficit during the 1st min of muscular exercise is imposed by the steady-state energy requirement whatever the type of exercise. The smaller energy expenditure during this phase is probably due to less energy being released when creatinge phosphate is split without resynthesis (O2 deficit) than during splitting and resynthesis of high-energy phosphate bonds (steady state).

Body Temperature Regulation↗

Modifications of glucose storage and oxidation in nonobese diabetics, measured by continuous indirect calorimetry.

A new application of continuous indirect calorimetry is described for measuring the disposal of a glucose load. In a group of 10 normal subjects, 3 h after a 100 g oral glucose load, 20 g glucose was oxidized at basal rate, 19 g in response to the load and 63 g stored, while a decrease of 2 g was observed in the glucose space (GS). In a group of four type I, insulin-dependent diabetics, both glucose oxidation (9 g at the basal rate and 4 g in response to the load) and glucose storage (9 g) were markedly decreased, with the remainder either being lost in the urine (36 g) or remaining in the glucose space (42 g). In a group of eight nonobese type II, non-insulin-dependent diabetics, glucose oxidation both in the basal rate and in response to the load was slightly decreased (13 and 14 g, respectively) and glucose storage decreased to 40 g. These results suggest that, in type I diabetics, complete insulin deficiency seriously impairs two major mechanisms regulating glucose homeostasis, i.e., glucose storage and oxidation, while, in type II diabetics, the remaining insulin secretion attentuates these disturbances.

Adolescent↗

Substrate utilization during prolonged exercise after ingestion of 13C-glucose in obese and control subjects.

This study was performed to investigate whether the difference in substrate utilization observed between obese and control individuals at rest still exists during prolonged exercise. Using a combination of respiratory exchange and tracer techniques, six obese and six control subjects were investigated while exercising for 2 h on a bicycle ergometer, 1 h after ingesting 100 g naturally-enriched 13C-glucose. Oxidation rates of protein, lipid and carbohydrate (CHO) were measured by indirect calorimetry and that of exogenous glucose by mass spectrometry (13CO2). Before exercise the obese subjects presented a lower rate of CHO utilization with a mean respiratory quotient of .803 compared to .858 for the controls. This impairement of CHO utilization disappeared during exercise where total CHO oxidation was found to be comparable for the obese (94.0 +/- 8.4 g) and the control group (94.3 +/- 6.1g). Exogenous-glucose oxidation was even slightly more elevated in the obese subjects (33.6 +/- 2.5 g compared with 28.1 +/- 2.3 g). Two hypotheses have been proposed to explain the improvement in CHO utilization during exercise after a glucose load: (1) The fall in FFA is sufficient to suppress the inhibition of CHO uptake and oxidation; (2) The insulin resistance decreases during exercise. In conclusion, this study supports the concept that exercise performed by obese individuals stimulates CHO utilization with a concomitant improvement in glucose tolerance.

Adult↗

Need for beta-blockade in hypertension reduced with long-term minoxidil.

Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients.

Adrenergic beta-Antagonists↗

The comparative oxidation of glucose, fructose, sorbitol and xylitol in normal man.

The aim of the study was to compare the effects of fructose, sorbitol and xylitol with those of glucose on blood glucose and insulin levels and carbohydrate utilization in man. The experiment was performed by means of continuous indirect calorimetry in five groups of five to six normal volunteers during infusion of either glucose, fructose, sorbitol, xylitol or a mixture of fructose, glucose and xylitol in the proportion of 2:1:1. Glucose and insulin did not present any important variations during the fructose, sorbitol and xylitol infusiosns. However, carbohydrate oxidation rose significantly during administration of these substrates. Carbohydrate oxidation rose 80 mg/min for fructose, 27 mg/min for sorbitol, 39 mg/min for xylitol and 75 mg/min for the carbohydrate mixture, in comparison to 101 mg/min for glucose. It is concluded that fructose, sorbitol and xylitol provoke an increase in carbohydrate utilization without a corresponding rise in glycemia and insulinemia.

Adult↗