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.

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.

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.

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.

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.

Liver and muscle glycogen content after glucose infusion in dogs.

The purpose of the present work was to determine the changes in the liver and muscle glycogen content during and after glucose infusion to elucidate tissue distribution of glucose in dogs. Glucose was infused intravenously during 2 hours in a dose of 1.7 mM . kg-1 . min-1. At designated time intervals venous blood samples were taken for determinations of glucose concentration, and the liver as well as muscle tissue samples were taken using a needle biopsy technique for determination of glycogen content. Liver glycogen content was increased significantly already at 30 th min of glucose infusion, and 60 min after termination of the infusion, it was by 53.1 +/- 0.58 and 174.3 +/- 48.3 mM glucosyl units per kg of wet liver higher than the initial value. Muscle glycogen content was also increasing progressively during the whole period of glucose infusion, and 1 h after termination of the infusion it was by 30.8 +/- 2.5 mM glucosyl units per kg of wet muscle above the initial value. It was calculated that 24.7 per cent of the glucose infused to dogs was stored as liver glycogen and 63.4 per cent as muscle glycogen.

Normal values of glycogen content in the dog skeletal muscle and liver.

Glycogen content was measured in the dog quadriceps femoris muscle and liver tissue under resting conditions after 24 h fasting period, using small tissue samples taken by a needle biopsy technique. The glycogen content in the quadriceps femoris ranged from 35.3 to 60.2 mM glucosyl units per kg of wet muscle with a mean of 50.0 +/- (SE) 1.2. The mean value of the liver glycogen content was 235.0 +/- 19.4 mM glucosyl units per kg of wet liver tissue with the average 121.1--316.1 mM glucosyl units per kg of wet tissue. It was calculated that approximately 127 mM glucosyl units of the glycogen is stored in the dog liver.

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.

Metabolic responses to adrenaline and muscle glycogen content in dogs treated with thyroxine.

Lipolytic, hyperglycaemic and lactacidaemic responses to 1h adrenaline infusion (0.1 microgram/kg/min) were compared in resting dogs before (control) and after prolonged thyroxine (T4) treatment. Besides, the effect of 2-week thyroxine administration on muscle glycogen content, and its changes following adrenaline infusion were examined. Prolonged T4-treatment of dogs resulted in considerable alterations of the metabolic actions of adrenaline. A marked difference between the control and T4-treated dogs was also found in the muscle glycogen content, which was significantly lower in the latter. Both in the control and T4-injected dogs adrenaline infusion caused similar depletion of the muscle glycogen store. However, in all the control animals examined supercompensation of muscle glycogen was noted 1 h following termination of adrenaline infusion, whereas T4-treated dogs were unable of incurring any significant muscle glycogen deposition.

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.

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 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.

Post-exercise changes in muscle glycogen content and blood metabolites in the dogs treated with triiodothyronine.

Post-exercise changes in muscle glycogen content and blood metabolites in the dogs treated with triiodothyronine. Acta Physiol. Pol., 1979, 30 (2) : 241--252. Prolonged T3-treatment markedly affected muscle glycogen content which was significantly lower than in controls both under resting conditions and after prolonged exercise. The post-exercise rate of the muscle glycogen resynthesis was inhibited in comparison with controls. Glucose (about 35 g per animal) infused to these dogs after cessation of exercise was able to bring about the rate of glycogen resynthesis to control values, but only during the first few hours of the recovery period. The present investigations confirmed that an excess of thyroid hormones elevates the lipolytic and lactacidemic responses to physical effort, but the pattern of the post-exercise changes in blood FAA and LA levels was similar in both groups. No differences between the control and T3-treated animals were found in the levels of blood catecholamines and insulin before, during and after exercise. Blood glucose level was significantly higher in T3-treated dogs at rest and markedly lower at the end of exercise in comparison with controls. The pattern of changes in BG level during the post-exercise period was similar in both animal groups.

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.

Metabolic responses to catecholamines in dogs injected with a single dose of triiodothyronine.

Lipolytic and glycogenolytic responses to catecholamine infusions were studied in resting dogs before and 20 h following administration of a single dose (0.1 mg/kg) of triiodothyronine (T3). In the dogs pretreated with T3 much higher increases in the plasma FFA concentration were found both during noradrenaline and adrenaline infusions in comparison with control experiments. Adrenaline-induced increases in blood LA and glucose levels were also significantly higher in T3-pretreated dogs than in controls. The blockade of beta-adrenergic receptors with propranolol prevented the increases in blood FFA and LA concentrations during subsequent adrenaline infusion. Phentolamine -- the alpha-adrenergic blocking agent -- infused to the T3-pretreated dog inhibited the adrenaline-induced rise in blood glucose level. The observed changes in the metabolic responses to catecholamines induced by triiodothyronine pretreatment indicate that at least in the dog this hormone potentiates both the lipolytic and glycogenolytic effects of catecholamines acting on appropriate adrenergic receptors.

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.