Metabolic and hormonal responses to adrenoceptor antagonists in 48-hour-starved exercising rats.

The influence of 48 hours of starvation on sympathoadrenal regulation of nutrient utilization was investigated in rats. To assess the role of alpha- and beta-adrenoceptors, rats were studied during alpha- and beta-blockade. Energy metabolism was measured using indirect calorimetry before, during, and after moderate swimming exercise (approximately 60% maximal O2 consumption [VO2max]). Additionally, blood samples were taken for determination of nutrient and hormone concentrations. In 48-hour-starved rats, under baseline conditions, there was a reduction in energy expenditure (EE) accompanied by a shift toward fat oxidation (fat-ox) in comparison to fed rats. Exercise-induced responses in EE, fat-ox, and carbohydrate oxidation (CHO-ox) did not differ from those in fed rats. In starved rats, a stronger response to exercise of the sympathoadrenal system was observed. In comparison to control 48-hour-starved rats, blockade of alpha- and beta-adrenoceptors led to a reduction in the exercise-induced increase in EE and fat-ox. The rate of CHO-ox was slightly reduced after blockade of either adrenoceptor type. Alpha-blockade prevented the exercise-induced increase in blood glucose. Plasma free fatty acid (FFA) was not affected. Blood lactate, plasma insulin, norepinephrine (NOR), and epinephrine (EPI) were increased after alpha-blockade. Due to beta-blockade, exercise-induced increases in glucose and FFA were prevented. Blood glucose even declined below the baseline value. EPI showed an exaggerated increase, and NOR showed a smaller increase. Results obtained in starved rats support the idea that alpha-adrenoceptor blockade-induced changes in energy metabolism are the result of a diminished oxygen supply due to diminished circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism.

Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy metabolism in normal controls and in streptozotocin-induced diabetic rats. Indirect calorimetry was applied before, during, and after moderate swimming exercise. Blood was sampled by means of a heart catheter for determination of nutrient and hormone concentrations. In islet transplanted rats, the results from indirect calorimetry and the nutrient and hormone concentrations were similar to the results in normal controls. In resting diabetic rats, insulin levels were very low, while glucose levels were exaggerated. Compared to resting controls, fat oxidation and energy expenditure were elevated, but carbohydrate oxidation was similar. Exercise increased energy expenditure and was similar in diabetic and control rats. Carbohydrate oxidation was lower and fat oxidation was higher in diabetic than in control rats. Exercise-induced increments in glucose, lactate and non-esterified fatty acid levels were the highest in diabetic rats. Thus, at rest, but not during exercise, insulin influences energy expenditure. Insulin reduces lipolysis and glycogenolysis. It enhances the relative contribution of carbohydrate oxidation and reduces fat oxidation to total energy expenditure, at rest and during exercise. Absence of insulin enhances anaerobic glycolytic pathways during exercise. It is concluded that in diabetic rats, islet transplantation of 50% of the normal pancreatic endocrine volume successfully normalizes insulin levels and hence energy metabolism at rest and during exercise.

Metabolic and hormonal responses to adrenoceptor antagonists in exercising rats.

alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta-adrenoceptor blockade. Energy metabolism was studied by means of indirect calorimetry before, during, and after moderate swimming exercise. Blood samples were taken for the determination of nutrient and hormone concentrations. In addition, central venous blood samples were withdrawn for determination of blood gases, pH, and total hemoglobin concentration (c/Hb). alpha- and beta-adrenoceptor blockade decreased the rates of energy expenditure (EE) and fat oxidation (fat-ox) during and after swimming in comparison to swimming without adrenoceptor blockade. The oxidation of carbohydrates (CHO-ox) was increased in both cases. alpha-Blockade prevented the exercise-induced increase in blood glucose, plasma free fatty acids (FFA) were not affected, and plasma insulin, norepinephrine (NOR), epinephrine (EPI), and lactate were markedly increased. beta-adrenoceptor blockade prevented the exercise-induced increases in blood glucose and FFA. EPI increased slightly more than and NOR less than in the control experiment. The exercise-induced decrease in insulin was more pronounced after beta-blockade. alpha-Blockade caused a less pronounced decrease in venous oxygen saturation (SO2) and tension (PO2) than in the control experiment. The exercise-induced increase in carbon dioxide tension (PCO2) was almost absent. After beta-blockade, venous SO2 and PO2 decreased more and PCO2 increased more than in the control experiment. It is concluded that both alpha and beta-blockade restrict the rate of EE during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Co-released adrenaline markedly facilitates noradrenaline overflow through prejunctional beta 2-adrenoceptors during swimming exercise.

The effect of intravenously applied (-)-adrenaline, taken up by and released from sympathetic nerves, on swimming exercise-induced noradrenaline overflow in permanently cannulated adrenal demedullated rats was studied. Adrenaline (100 ng/min) was infused for 2 h, during which a plasma concentration of 500 pg/ml (approximately 2.5 nM) was reached. One hour later plasma adrenaline had returned to undetectable levels. During swimming, adrenaline was released into the plasma in concentrations up to 133 pg/ml and the noradrenaline concentration was markedly enhanced as well. The total catecholamine increase amounted to 178% of control (saline infusion) in the first 3 min of swimming and 165% for the whole 20 min. Cocaine (2.5 mg/kg plus 0.05 mg/kg/min), infused together with adrenaline and continued throughout the experiment, prevented the exercise-induced release of adrenaline and no increase in plasma noradrenaline concentration was observed. Yohimbine (0.25 mg/kg) strongly further enhanced the exercise-induced overflow of both noradrenaline and adrenaline. This further increase was completely blocked by the selective beta 2-adrenoceptor antagonist ICI 118,551 ((+/-)-1-[(2,3-dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyleth yl) amino]-2-butanol) (1.0 mg/kg). These results demonstrate that adrenaline can be taken up by sympathetic nerve endings through cocaine-sensitive uptake carriers and is released from these nerves during swimming exercise. Neuronally released adrenaline markedly enhances exercise-induced catecholamine overflow through activation of prejunctional beta 2-adrenoceptors.

Methods for measurement of energy expenditure and substrate concentrations in swimming rats.

A measuring system is described for the determination of oxygen consumption (Vo2) and carbon dioxide production (Vco2) in swimming rats. Vo2 and Vco2 were measured by means of an O2-analyzer (Ametek S3A) and a mass spectrometer (Balzers QMG 511), respectively, combined with a gas flow meter. The measurements were made in a 5-1 metabolic chamber on top of a swimming pool in which a water flow of 0.22 m/s was maintained. The rats were fitted with an indwelling catheter with its tip at the entrance of the right atrium for the repeated determination of energy substrate and hormone concentrations, before, during, and after swimming. The inaccuracy of the Vo2 and Vco2 measurements was 0.18% and 0.31% of the reading, respectively; the imprecision was 2.15% and 2.59%. This high accuracy and precision of the system was attained by measuring room air for 20 s after each 100 s of measuring air from the metabolic chamber, and by using demineralized water in the swimming pool. Vo2 during steady-state swimming was 1.89 +/- 0.06 mmol/kg.min (ca. 60% Vo2max), indicating moderate exercise. Respiratory quotient (RQ), during steady-state exercise, was 0.80 +/- 0.01. Vo2 and RQ resulted in rates for carbohydrate and fat utilization of 15.6 +/- 0.8 and 15.1 +/- 0.7 mg/kg.min, respectively.

Effects of long-term d-fenfluramine treatment on energy metabolism in rats.

The effects of chronic intragastric administration of the anorectic agent d-fenfluramine on energy metabolism and nutrient concentrations were investigated at rest and during swimming. Rats were provided with permanent cannulas for blood sampling and intragastric administration of d-fenfluramine or saline. Energy expenditure and nutrient and hormone concentrations were determined. Under baseline conditions, d-fenfluramine increased carbohydrate utilization (14.2 vs. 7.0 mg/kg.min) and decreased fat oxidation (2.8 vs. 5.5 mg/kg.min). Plasma free fatty acid concentration was decreased (0.29 vs. 0.55 mmol/l) and lactate and insulin concentrations were increased after d-fenfluramine treatment (0.64 vs. 0.37 mmol/l and 61 vs. 33 mU/l, respectively). The shift in nutrient utilization also occurred during swimming. The exercise-induced increase in blood glucose was reduced after d-fenfluramine (+0.8 vs. +2.0 mmol/l). During swimming, free fatty acid, lactate and insulin concentrations were similar in the two groups. It is hypothesized that chronic d-fenfluramine treatment increases in the oxidation of carbohydrates and decreases the oxidation of fat as a result of a decrease in the transport of fatty acids over the mitochondrial membrane.

The effect of epinephrine on oxygen consumption, overall energy metabolism, and substrate utilization in rats.

In this study the influence of epinephrine (E) on oxygen consumption, overall energy metabolism, and substrate utilization in rats has been investigated. Therefore E was infused at rates of 20, 35, and 50 ng/min for 40 min. Infusion of the solvent, saline, served as control experiment. Before, during, and after the infusion, VO2, as parameter for total metabolism, and RQ, as parameter for substrate utilization, were determined using an open circuit. In addition blood samples were taken for determination of blood glucose, plasma free fatty acids (EFA) and plasma insulin concentrations. The results show a rise in VO2 and blood glucose during infusion of E. Plasma FFA concentrations were elevated during infusion of E and of saline. Plasma insulin decreased when E was administered. RQ values were increased when E was infused at rates of 35 and 50 ng/min. The results suggest that E can influence the ratio in which glucose and FFA are utilized. This influence seems to be excerpted indirectly by influencing the availability of the substrates, rather than directly, by influencing utilization.

Phosphorylation of low molecular mass cytosolic proteins by protein kinase C and protein kinase A in the rabbit exocrine pancreas.

Subcellular fractionation of rabbit pancreatic acini was performed to study the distribution of endogenous substrates for protein kinase C. Substrates for protein kinase C were found to be predominantly low molecular mass proteins of cytosolic origin. At least three of these soluble substrates, with molecular masses of 17-19 kDa, were relatively heavily phosphorylated by endogenous as well as purified pancreatic protein kinase C. In the same molecular mass range, 16-18 kDa, soluble proteins were also phosphorylated by protein kinase A. Moreover, addition of cyclic AMP under conditions that activated protein kinase C gave a more than additive labelling of these low molecular mass proteins. The latter observation may be of interest in view of the potentiating effect cyclic-AMP-activated protein kinase A has on amylase secretion stimulated by secretagogues which increase free cytosolic Ca2+ and activate protein kinase C.