Effect of triiodothyronine (T3) excess on fatty acid metabolism in the soleus muscle from endurance-trained rats.

We studied whether short-term administration of triiodothyronine (T3) for the last 3 days of endurance training would influence the rate of uptake of palmitic acid (PA) as well as metabolism in rat soleus muscle, in vitro. Training per se did not affect the rate of PA uptake by the soleus; however, an excess of T3 increased the rate of this process at 1.5 mmol/L PA, as well as the rate that at which PA was incorporated into intramuscular triacylglycerols (TG). The rate of TG synthesis in trained euthyroid rats was reduced after exercise (1.5 mmol/L PA). The rate of PA oxidation in all of the trained rats immediately after exercise was enhanced by comparison with the sedentary values. Hyperthyroidism additionally increased the rate of this process at 1.5 mmol/L PA. After a recovery period, the rate of PA oxidation returned to the control values in both the euthyroid and the hyperthyroid groups. Examination of the high-energy phosphate levels indicated that elevated PA oxidation after exercise-training in euthyroid rats was associated with stable ATP levels and increased ADP and AMP levels, thus reducing energy cellular potential (ECP). In the hyperthyroid rats, levels of ADP and AMP were increased in the sedentary as well as the exercise-trained rats. ECP levels were high as a result of high levels of ATP and decreased levels of ADP and AMP in hyperthyroid rats after the recovery period. In conclusion, short-term hyperthyroidism accelerates PA utilization in well-trained soleus muscle.

Effect of a short-term dietary creatine supplementation on high-energy phosphates in the rat myocardium.

The aim of this study was to find out whether creatine (Cr) feeding affects total creatine (TCr), phosphocreatine (PCr), adenine nucleotide contents and beta-hydroxy-acyl-CoA-dehydrogenase (HAD) activity in myocardium as compared to red skeletal muscle. Ten adult Wistar rats received Cr (2.5% of diet weight) for 7 days. In Cr fed rats, PCr was increased (by approx. 20%) in cardiac and in soleus muscles with ATP elevated in myocardium and TCr and free Cr in soleus. In both muscles, Cr feeding enhanced HAD activity. It is concluded, that dietary Cr does increase cardiac muscle high energy phosphate reserves and its oxidative potential.

Lipid peroxides production after strenuous exercise and in relation to muscle morphology and capillarization.

The antioxidative capacity of slow twitch muscle fibers has been reported to be higher than that of fast twitch ones. The purpose of this study was to relate the production of lipid peroxides during exercise to the morphology and capillarization of human muscles. Twenty-seven healthy volunteers performed a strenuous 90-min exercise. The content of malonyldialdehyde (MDA) in the middle portion of vastus lateralis muscle was found positively correlated with percentage and the relative cross-sectional area of the type 1 of muscle fibers (r = 0.46, P < 0.05, r = 0.43, P < 0.05, respectively) but negatively with type II muscle fibers (r = -0.46, P < 0.05, r = -0.43, P < 0.05, respectively), especially type IIB. The content of MDA in the vastus lateralis muscle correlated positively with the number of capillaries around type II muscle fibers (r = 0.71, P < 0.001). It is suggested that the production of lipid peroxides parallels the exercise-induced increase of oxygen uptake in the muscle, being highest in more oxidative and better perfused, oxygen-consuming muscle fibers.

Muscle metabolism during exercise in dogs after 8-week confinement.

NASA: Several indicators of muscle metabolism were measured in dogs during exercise following 8 weeks of confinement in cages. Muscle tissue samples were studied at rest and following exercise for adenine nucleotides, creatine phosphate, creatine, glycogen, pyruvate, and lactate. Results indicate that confinement results in less efficient metabolic responses to exercise, decreased muscle glycogen at rest, and changes in the equilibrium between ATP breakdown and resynthesis during exercise.^ieng

Effects of hyperinsulinemia on muscle fiber composition and capitalization in rats.

Statistical studies repeatedly have shown an association between systemic insulin resistance and a preponderance of highly glycolytic, relatively insulin-insensitive muscle fibers as well as a low density of muscle capillaries. The nature of the relationship between these observations is, however, not clear. Female rats were made hyperinsulinemic for 7 days by implantation of osmotic minipumps. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy was controlled with glucocorticoid substitution. This resulted in hyperinsulinemia and moderate hypoglycemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity was increased and measured with a hyperinsulinemic-euglycemic clamp technique. This was paralleled by an elevated glucose utilization estimated as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and inguinal adipose tissues and the soleus and extensor digitorum longus muscles. Glycogen synthesis was also elevated in the soleus muscle. Muscle fiber composition changed with hyperinsulinemia and elevated 2-deoxyglucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminished. Capillary density was elevated per unit muscle surface area as well as per muscle fiber. This was paralleled by increased insulin sensitivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber composition is of importance for insulin sensitivity in muscle.

Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats.

The effects of testosterone on insulin sensitivity were studied in oophorectomized female rats. Euglycemic, hyperinsulinemic clamp measurement showed a marked decrease of insulin sensitivity after 48 but not 24 h of testosterone exposure, which was overcome at high insulin concentrations. Insulin stimulation of 2-deoxyglucose uptake as well as glycogen synthesis was measured in the white and red parts of the gastrocnemius, the extensor digitorum longus, and soleus muscles as well as in the liver (only glycogen synthesis). After 24 h of treatment, inhibition of both 2-deoxyglucose uptake and glycogen synthesis was found in the most insulin-sensitive muscles. After 48 h of insulin stimulation, glycogen synthesis was inhibited in all examined individual muscles (white and red parts of gastrocnemius, extensor digitorum longus, and soleus) as was the activity of the insulin-sensitive part of glycogen synthase in muscle. Inhibition of insulin-stimulated 2-deoxyglucose uptake again affected the most insulin-sensitive muscles. There was a slight but significant change of muscle fiber composition toward less long-chain myosin and more short-chain myosin-containing fibers. Serum cortisol, plasma free fatty acids, and blood glycerol did not change. It is concluded that testosterone administration in moderate doses to oophorectomized female rats is followed by a rapid deterioration of insulin sensitivity in muscle, mediated mainly by perturbations of the insulin receptor-glycogen synthesis systems apparently coinciding with changes in muscle morphology.

Dynamics of metabolic responses to prolonged elevation of circulating adrenaline in resting and exercising rats.

The purpose of this study was to follow the time course of metabolic responses to hyperadrenalinemia sustained up to 3 days. Hyperadrenalinemia was produced in rats by s.c. implantation of tablets releasing adrenaline (A) at a constant rate (1.6 micrograms x min-1). After 6, 12, 24 and 72 h of hyperadrenalinemia and 3 days after the tablet removal rats were sacrificed and liver, 3 types of muscles and blood samples were taken. Each time 14 rats were used: 7 of them were sedentary and 7 performed treadmill endurance exercise before decapitation. Sham operated animals served as controls. In preliminary experiments working ability was examined in 10 hyperadrenalinemic and 10 control rats. Duration of exercise until exhaustion was reduced in hyperadrenalinemic rats on the average by 40%. In sedentary rats, hyperglycemia, marked depletion of liver glycogen (by approx. 80%) and muscle glycogen (by 60-80%) as well as an elevation (2-4 times) of muscle lactate (LA) were found only during the first day after A-tablet implantation. At the end of the experiment these values approached the control ones. Muscle contents of ATP and creatine phosphate (CrP) were decreased by approx. 20% and 30-60%, respectively. Plasma FFA were markedly enhanced, varying in the time-course of the experiment from 0.8 to 1.4 mmol x l-1. Post-exercise values for blood glucose, liver and muscle glycogen were always lower in hyperadrenalinemic rats than in controls sacrificed after time-matched exercise (30 min). Circulating FFA decreased during exercise at all time points following A-tablet implantation, but they were still above the post-exercise levels in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormones and muscle metabolism in dogs.

Muscle contents of ATP, ADP, AMP, creatine phosphate and creatine as well as glycogen, some glycolytic intermediates, pyruvate and lactate were compared in the intact, thyroidectomized and triiodothyronine (T3) treated dogs under resting conditions. After thyroidectomy muscle glycogen, glucose 1-phosphate and glucose 6-phosphate contents were significantly elevated while in T3-treated animals these variables were decreased in comparison with control dogs. Muscle free glucose was not altered by thyroidectomy but T3 treatment significantly increased its content. Muscle lactate content was elevated both in hypo- and hyperthyroid animals. Muscle ATP and total adenine nucleotide contents were significantly increased in hyperthyroid dogs while no differences were found between the three groups in the muscle creatine phosphate content. It is assumed that in T3-treated animals carbohydrate catabolism is enhanced in the resting skeletal muscle in spite of high tissue ATP content. Muscle metabolite alterations in hypothyroid dogs seem to reflect the hypometabolism accompanied by a diminished rate of glycogenolysis with inhibited rate of pyruvate oxidation or decreased rate of lactate removal from the cells.

Thyroid hormone deficiency and muscle metabolism during light and heavy exercise in dogs.

Muscle glycogen, glycolytic intermediate and high energy phosphate contents were compared in 5 intact-control (C) and thyroidectomized (THY) dogs after 30 min treadmill exercise of low (40W) and high (70W) intensities. Although after the exercise of relatively low intensity the rate of glycogenolysis and muscle lactate accumulation in THY dogs exceeded those in controls, the diminished oxidative capacity in the former was inadequately compensated, resulting in lowering of APT and CrP contents. At the higher work load the latter effects were more pronounced while the rate of glycogenolysis was similar or even lower than in controls. Inadequate fuel utilization may be considered as a factor limiting ability for heavy exercise in hypothyroidism.

Prolonged hyperadrenalinemia impairs exercise ability in rats.

This study was performed on rats with sustained (24 h) hyperadrenalinemia produced by sc implantation of retard adrenaline (A) tablets. Comparing with control, sham-operated animals, in A-treated rats duration of endurance exercise until exhaustion was shortened by approx. 40%. This was accompanied by: significant decreases of the pre-exercise muscle glycogen and creatine phosphate values in both "slow twitching" (soleus) and "fast twitching" (white portion of gastrocnemius) muscles, and of ATP content in soleus. Muscle lactate and pyruvate contents as well as blood glucose and FFA levels were elevated. After exercise muscle substrate and metabolite contents were similar in both groups in spite of the difference in exercise duration. It is concluded that prolonged hyperadrenalinemia diminishes the intramuscular energy substrate content, thereby reducing endurance capacity of rats.

Muscle metabolism during prolonged physical exercise in dogs.

In order to provide reference data, adenine nucleotide, creatine phosphate, glycogen, glycolytic intermediates and lactate muscle contents were measured in 49 dogs under resting conditions and during prolonged physical exercise of moderate intensity performed until exhaustion. Both the resting and exercise values of the measured variables were remarkably similar to those described in human subjects, except muscle lactate content which achieved higher values during submaximal exercise in dogs than in men.

Work performance, thermoregulation and muscle metabolism in thyroidectomized goats (Capra hircus).

1. Thyroid hormone deficiency resulted in a markedly diminished work efficiency of goats exercising on a treadmill at an ambient temperature of 30 degrees C. 2. The close relationship between the exercise-induced increase in core temperature and the magnitude of evaporative heat loss, characteristic for intact animals, was nearly completely abolished after thyroidectomy. 3. Muscle glycogen utilization and lactic acid accumulation during exercise were enhanced in thyroidectomized animals in spite of the lower work rate and shorter duration of exercise in comparison with euthyroid goats.

Exercise hyperthermia as a factor limiting physical performance: temperature effect on muscle metabolism.

The muscle contents of high-energy phosphates and their derivatives [ATP, ADP, AMP, creatine phosphate (CrP), and creatine], glycogen, some glycolytic intermediates, pyruvate, and lactate were compared in 11 dogs performing prolonged heavy exercise until exhaustion (at ambient temperature 20.0 +/- 1.0 degrees C) without and with trunk cooling using ice packs. Without cooling, dogs were able to run for 57 +/- 8 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 +/- 0.2 and 43.0 +/- 0.2 degrees C, respectively. Compared with noncooling, duration of exercise with cooling was longer by approximately 45% while Tre and Tm at the time corresponding to the end of exercise without cooling were lower by 1.1 +/- 0.2 and 1.2 +/- 0.2 degrees C, respectively. The muscle contents of high-energy phosphates (ATP + CrP) decreased less, the rate of glycogen depletion was lower, and the increases in the contents of AMP, pyruvate, and lactate as well as in the muscle-to-blood lactate ratio were smaller. The muscle content of lactate was positively correlated with Tm. The data indicate that with higher body temperature equilibrium between high-energy phosphate breakdown and resynthesis was shifted to the lower values of ATP and CrP and glycolysis was accelerated. The results suggest that hyperthermia developing during prolonged muscular work exerts an adverse effect on muscle metabolism that may be relevant to limitation of endurance.

Mechanism of sympathetic activation during prolonged physical exercise in dogs. The role of hepatic glucoreceptors.

It seems likely that depletion of body carbohydrates may account for the rise in the sympathetic activity during prolonged exercise, since glucose given during or before exercise reduces the increase in plasma catecholamines. The aim of the present study was to find out whether the increase in plasma noradrenaline (NA) in response to exercise can be reduced by 1. increasing of the amount of carbohydrate available for metabolism without producing hyperinsulinemia and 2. by inhibition of afferent activity from hepatic glucoreceptors. The study was performed on dogs which exercised whilst receiving either the intravenous fructose infusion (2.2 mmol/min) or a slow glucose infusion (0.25 mmol/min) which was given either via the portal or a peripheral vein. Fructose infusion reduced the muscle glycogen depletion during exercise and reduced the increase in plasma NA and glycerol concentrations without altering the blood glucose or insulin levels. The exercise-induced increases in plasma NA and glycerol concentrations were significantly smaller with intraportal than with peripheral glucose infusion but there were no differences between these two cases in the concentration of glucose in the systemic circulation. These findings indicate that the reduction of the plasma NA response to physical effort under conditions of increased carbohydrate availability cannot be attributed to the inhibitory effect of insulin on sympathetic activity and provide evidence for the participation of hepatic glucoreceptors in the control of the sympathetic activity during exercise.

Effect of prolonged exhausting exercise on the adrenal cortex response to ACTH.

Plasma cortison response of ACTH injection was studied in dogs under control conditions and after a prolonged exercise performed until exhaustion. Exercise induced a marked increase in plasma cortisol concentration but no significant differences were found in the level of plasma cortisol following ACTH injection between the control and post-exercise animals.

Physiological responses to prolonged physical exercise in dogs.

1. Duration of exercise until exhaustion is significantly correlated with body weight of dogs. 2. Rectal temperature (Tre) achieved at the end of the effort depends on the resting value of Tre, but the exercise-induced increases in Tre are unrelated to the initial Tre. 3. The magnitude of exercise-induced decrease in blood glucose (BG) level is positively correlated with the resting BG level and negatively correlated with the elevations of the plasma free fatty-acid (FFA) concentration. 4. A significant positive relationship is found between the exercise-induced increases in the plasma FFA levels and noradrenalinaemia.

Low muscle and liver glycogen contents in dogs treated with thyroid hormones.

Muscle biopsies for glycogen determinations were taken from dogs before (controls) and after prolonged treatment with thyroid hormones (T4 or T3). The glycogen content in quadriceps femoris was measured before exercise, immediately after its cessation, and during 24h of post-exercise recovery. The effect of thyroxine treatment on the liver glycogen content both at rest and following physical effort was also studied. A marked decrease in the muscle glycogen content determined at rest was found both in T4 and T3-treated dogs in comparison with controls. Physical exercise diminished the muscle glycogen store to similar values in control and thyroid hormone-treated dogs, but the rate of the muscle glycogen utilization during exercise was lower in the latter. The rate of the post-exercise muscle glycogen synthesis was considerably inhibited in thyroid hormone-treated dogs, but 1 hr glucose infusion, applied immediately after cessation of exercise, accelerated the rate of glycogen re-synthesis, so it was close to that in controls without infusion. Thyroxine treatment also affected the liver glycogen store. Both at rest and after physical exercise significantly lower liver glycogen contents were found in T4-treated dogs than in controls.

Effect of thyroxine treatment on metabolic responses to a single insulin injection.

Metabolic responses to a single i.v. injection of cristalline insulin (0.2 i.u./kg b.w.) were compared in control and T4-treated dogs both at rest and after prolonged physical exercise. The post-insulin decrease in blood glucose was significantly correlated with the pre-insulin BG concentration. Thus, the insulin-induced fall of BG was greatest in T4-treated dogs at rest, in which significantly higher BG levels were found in comparison with controls, and smallest in the same dogs after exercise, i.e. at the lowest initial BG concentrations. The post-insulin hypoglycaemia caused marked increases in the plasma FFA level in control dogs, both at rest and after physical effort, and in T4-treated dogs at rest. They were accompanied by elevations in the plasma adrenaline levels. In T4-treated dogs given insulin after exercise decreases both in the plasma FFA and A concentrations were found. In the majority of the control and T4-treated dogs insulin injected at rest caused an increase in blood LA levels, being more pronounced in the latter. Insulin injected after physical exercise did not change blood LA level in T4 treated dogs, and it caused its decrease in the control animals. The results of these investigations show that both T4-treatment and physical exercise, performed prior to insulin injection, modify the metabolic response to insulin and post-insulin hypoglycaemia.

Diminished adrenergic response to 2-deoxy-D-glucose after prolonged, exhausting physical exercise in dogs.

Effect of 2-deoxy-D-glucose (2DG) on plasma adrenaline, glucose and free fatty acid concentrations was studied in dogs under control conditions and after prolonged, exhausting physical exercise. The increase in all three variables in response to 2DG was significantly reduced following the exercise. The results suggest diminished responsiveness of adrenal medulla to the glucopenic stimulus after exhausting exercise.