Biomedical subjects

W W Winder

Publications and source records attributed to W W Winder.

At least 91 records · Page 5Linked to original sources

PubMed1984

Mechanism of training-induced attenuation of postexercise ketosis.

We have examined the roles of liver glycogen and malonyl coenzyme A (CoA) in determining the degree of postexercise ketosis in endurance-trained and nontrained rats. Three groups of rats were run on a treadmill for 90 min: trained (2 h/day, 6 wk) and food restricted to 5.5 g/100 g body wt the night before the 90-min exercise bout (group 1), nontrained fed ad libitum (group 2), and nontrained food restricted (same as trained) (group 3). Liver glycogen was 34 +/- 5, 24 +/- 2, and 7 +/- 2 mg/g in groups 1, 2, and 3, respectively, at the end of exercise. At the end of exercise and during the postexercise period the blood 3-hydroxybutyrate concentration in group 3 was significantly higher than in groups 1 or 2. No difference was observed between groups 1 and 2 in blood 3-hydroxybutyrate. Hepatic malonyl CoA was decreased to the same extent in all rats during exercise but remained depressed only in the glycogen-depleted group 3 rats in the postexercise period. These data suggest that the differences in degree of ketonemia in the postexercise period (but not during exercise) were due to lower hepatic malonyl CoA in group 3 rats.

3-Hydroxybutyric Acid↗

PubMed1983

Tissue effects of iron deficiency in the rat.

Measurements of succinate dehydrogenase and mitochondrial glycerol-3-phosphate dehydrogenase activities, iron, cytochrome c and myoglobin, were made on various hind-leg muscles, fast-twitch red and white muscle and heart and liver of male Wistar rats fed an iron-deficient diet on weaning. Rats fed the same diet and given 20 mg iron intraperitoneally as iron-dextran (Imferon) served as controls. For iron-repletion studies anemic rats (hemoglobin less than 7 g/dl) were given a single injection of 10 mg iron (Imferon) and the time course of change in the above parameters was followed up to 22 days after injection. The iron concentration of most iron-deficient muscles dropped to approx. 35% of control, the heart to 60% and liver to 13%. On repletion, the iron concentration of all tissues increase significantly by 4 days. While the levels of cytochrome c and myoglobin approximated the iron levels in muscle, they did not change significantly in the heart. Succinate dehydrogenase activity dropped profoundly in muscle, to 10-30% of control; on repletion, the activity increased significantly. Mitochondrial glycerol-3-phosphate dehydrogenase activity showed only small changes in iron-deficient tissues.

Anemia, Hypochromic↗

PubMed1983

Decrease in liver norepinephrine in response to exercise and hypoglycemia.

The existence of the sympathetic innervation of the liver has been known for many years, but the role of this system in regulation of liver metabolism is unclear. The purpose of these experiments was to identify physiological conditions for activation of liver sympathetics. Liver norepinephrine (NE) was measured in normal resting rats and in rats exposed to swimming, treadmill running, fasting, and insulin-induced hypoglycemia. Liver NE decreased significantly in response to swimming (-71% of control), treadmill running (-53% of control), and hypoglycemia (-24% of control). Rats that are endurance trained by daily bouts of treadmill running for 3 mo show no decrease in liver NE in response to a 60-min run on the treadmill, whereas nontrained rats show a 50% decrease in liver NE with the same amount of exercise. We conclude that the liver sympathetics are activated in response to swimming, treadmill exercise and hypoglycemia, and that endurance training causes a reduction in the degree of exercise-induced activation of these neurons.

Animals↗

PubMed1983

Glycogenolytic rates and cAMP in livers of rats running at different treadmill speeds.

The purposes of this study were to determine the effect of different work rates on the rate of liver glycogenolysis and to determine the relationship between liver adenosine 3',5'-cyclic monophosphate (cAMP) levels and the glycogenolytic rate. Rats were run at treadmill speeds ranging from 10 to 34 m/min up a 15% grade for either 30 or 60 min. Both the magnitude of the decrease in liver glycogen and the increase in hepatic cAMP were dependent on the running speed and the duration of running. At the highest work rate a disproportionate acceleration in the liver glycogenolytic rate was observed compared with that at lower work loads, thus resulting in a curvilinear relationship between work rate and liver glycogenolytic rate. A high degree of correlation was found between the liver glycogenolytic rate and hepatic cAMP concentration (r = 0.98). This observation is consistent with the idea that hepatic glycogenolytic rates are determined by cAMP-mediated mechanisms.

Animals↗

PubMed1983

Adrenal hormones and liver cAMP in exercising rats--different modes of anesthesia.

We have compared five different modes of anesthesia (iv and ip pentobarbital sodium, ether, CO2, and cervical dislocation) with respect to their effects on liver glycogen, liver adenosine 3',5'-cyclic monophosphate (cAMP), blood glucose and lactate, plasma corticosterone, norepinephrine, and epinephrine in resting rats and in rats run on a treadmill at 26 m/min for 30 min. Ether, CO2, and cervical dislocation were found to be unsuitable due to the marked elevation in plasma catecholamines seen in both resting and exercising rats. Injection of pentobarbital sodium ip required an average of 8 min before onset of surgical anesthesia as opposed to less than 5 s for iv pentobarbital. Exercising rats anesthetized with ip pentobarbital showed markedly lower plasma catecholamines compared with rats given iv pentobarbital. Hepatic cAMP increased in response to exercise in all groups except the ip pentobarbital group. This is most likely due to the long delay between the end of the exercise and freezing of the liver in the ip pentobarbital-anesthetized animals. We conclude that iv injection of pentobarbital is the most suitable method of anesthesia for obtaining accurate measurements of plasma stress hormones, substrates, and metabolites and of hepatic cAMP and glycogen in resting and exercising rats.

Adrenal Cortex Hormones↗

PubMed1982

Endurance training attenuates stress hormone responses to exercise in fasted rats.

Endurance exercise training produces major adaptations in hormonal and metabolic responses to exercise. This study was designed to determine whether the differences in hormone response persist in the fasted condition when liver glycogen is depleted. Rats were run on a motor-driven rodent treadmill 5 days/wk for periods up to 2 h/day for 10 wk. Trained and nontrained rats were then fasted 24 h and were run for periods ranging from 0- to 60 min. At the end of 60 min of exercise muscle glycogen was higher in trained rats (2.9 +/- 0.3 vs. 1.1 +/- 0.1 mg/g). Blood glucose was maintained at higher levels in trained rats throughout the course of the exercise (3.2 +/- 0.1 vs. 2.3 +/- 0.1 mM after 60 min). Plasma concentrations of glucagon and epinephrine increased in both groups during the exercise but were significantly lower in trained animals. Differences between trained and nontrained animals in stress hormone responses to exercise persist in the fasted state and appear to be a consequence of the capacity of trained animals to maintain higher blood glucose levels.

3-Hydroxybutyric Acid↗

PubMed1981

Circulating reverse triiodothyronine in humans during exercise.

Circulating thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) as well as blood lactate and glucose concentrations were measured in a group of 12 trained volunteer subjects prior to and after swimming 0.18 or 0.9 km, to determine if increase in metabolic activity was accompanied by diversion of T4 monodeiodination from the active (T4 to T3) to the inactive (T4 to rT3) pathway. The resting T4, T3, and rT3 levels were 8.5 micrograms . 100 ml-1, 108 ng . 100 ml-1, and 57 ng . 100 ml-1, respectively, whereas after 0.18 km of swimming the corresponding levels were 9.5 micrograms . 100 ml-1, 135 ng. 100 ml-1 and 70 ng . 100 ml-1. After 0.9 km of swimming, T4, T3, and rT3 levels were 9.0 micrograms . 100 ml-1, 126 ng . 100 ml-1, and 66 ng . 100 ml-1, respectively. The swimming was accompanied by hemoconcentration and increase in blood lactate but not in glucose concentrations. In two other investigations thyroid hormones were measured prior to and after 60 or 90 min of moderate exercise on a bicycle ergometer. This exercise had no effect on circulating thyroid hormone levels. Free thyroxine (FT4) concentration and thyroxine binding globulin (TBG) capacity were unaltered after exercise. In conclusion, brief strenuous swimming or moderate bicycle exercise had minor or no effect on thyroid hormone concentrations when consideration was given to the attendant hemoconcentration. Even when exercise induced small T3 and rT3 changes were noted, they were in the same direction (increase) thus demonstrating a lack of diversion of peripheral T4 monodeiodination.

Adolescent↗

PubMed1981

Peripheral markers of thyroid status unaffected by endurance training in rats.

In order to more clearly define the relationship between endurance exercise training and thyroid activity we have measured T4 turnover in exercise-trained and sedentary rats under conditions of controlled food intake and body weight. Rats were run on rodent treadmills at gradually increasing speeds and durations until at the end of 12 weeks they were running 2 h per day at 31 m/min. Sedentary rats were either allowed to eat ad libitum or were food restricted so that they gained weight at the same rate as controls. Relative heart weight and plantaris citrate synthase activity were both significantly increased in trained animals compared to controls. The thyroxine secretion and degradation rates were not affected by the training. In addition, liver mitochondrial alpha-glycerophosphate dehydrogenase and citrate synthase were measured as indicators of the thyroid state at the tissue level. Neither of these enzymes were increased in the trained rats. We conclude that increased thyroid activity is not essential for inducing and maintaining the adaptations in muscle mitochondrial enzymes which occur in response to prolonged endurance exercise training.

Animals↗

PubMed1981

Physiological and biochemical effects of iron deficiency on rat skeletal muscle.

Young rats were made iron deficient by feeding them a low-iron diet for 8 wk. Iron deficiency resulted in a 50% decrease in cytochrome c and cytochrome oxidase and a 26% decrease in mitochondrial glycerol-3-phosphate dehydrogenase activity in skeletal muscle. Respiratory capacity of muscle homogenates was reduced 55%. After 8 days of iron treatment, respiratory capacity, cytochrome c, cytochrome oxidase, and glycerol-3-phosphate dehydrogenase had returned 50% toward normal. Maximum O2 uptake of contracting hindlimb muscles averaged 8.5 mumol O2.min-1.g-1 in control, 4.3 mumol O2.min-1.g-1 in iron-deficient, and 6.2 mumol O2.min-1.g-1 in the 8-day-iron-repleted rats. Muscle fatigue during 10 min of stimulation was greater in the iron-deficient group. Lactate concentration in red muscle was higher in iron-deficient than in control rats after stimulation. The muscle fatigue and lactate responses returned 50% toward normal during 8 days of iron treatment. We conclude that iron deficiency results in a decrease in skeletal muscle capacity for aerobic metabolism and, by this mechanism, increases susceptibility to fatigue.

Animals↗

PubMed1981

Adaptive responses of rats to prolonged treatment with epinephrine.

Rats were given a daily injection of L-epinephrine, 100 micrograms/100 g body wt, for 6 wk. The hearts of the epinephrine-treated animals were heavier (11.5%), and blood glucose and plasma insulin concentrations were lower than those of control rats. Acute responses to epinephrine were compared in the two groups. An increase in blood glucose and decreases in plasma insulin, liver glycogen, and muscle glycogen occurred in both groups. The magnitude of these responses were similar in the two groups except for the decrease in muscle glycogen, which was smaller in the chronic epinephrine-treatment group. There were no changes in respiratory capacity, citrate synthase or succinate dehydrogenase activities, or in cytochrome c concentration in skeletal muscle in response to 6 wk of epinephrine treatment. These results are compatible with the suggestion that catecholamines may play a role in some of the metabolic and cardiac adaptations to exercise training. However, they argue strongly against the hypothesis that catecholamines are responsible for inducing the increase in muscle mitochondria that occurs in response to exercise training.

Animals↗

PubMed1981

Effect of endurance training on liver cAMP response to prolonged submaximal exercise.

Endurance-trained rats utilize liver glycogen at a reduced rate during exercise compared to nontrained rats. We have compared liver cAMP responses to exercise in trained and nontrained rats in an attempt to elucidate the mechanism of this adaptation. Rats were trained on a motor-driven rodent treadmill 5 days/wk for 12 wk. On the day of the test, trained and nontrained rats were quickly anesthetized after running at 21 m/min up a 15% grade for periods up to 90 min. After 45 min of running, liver cAMP had increased from 0.60 +/- 0.01 to 0.90 +/- 0.03 pmol/mg in nontrained rats whereas no significant increase had occurred in livers of trained rats. Plasma glucagon and norepinephrine levels were significantly lower in trained rats at this point. At the end of 90 min hepatic cAMP was 1.28 +/- 0.12 in nontrained compared to 0.83 +/- 0.06 pmol/mg in trained rats. Plasma glucagon was markedly elevated in nontrained but not in trained rats at this time. The lower rate of liver glycogen utilization in trained rats is consistent with the lower cAMP levels maintained early in exercise.

Animals↗

PubMed1980

Contractile, biochemical, and histochemical properties of thyrotoxic rat soleus muscle.

The effects of thyrotoxicosis on the contractile properties of soleus muscle were examined in rats given 3 mg of T4 and 1 mg of T3 per kg of diet for 6--8 wk. Thyrotoxicosis induced significant decreases in isometric twitch contraction time (CT), one-half relaxation time, and peak twitch tension. The Ca2+ uptake activity of the sarcoplasmic reticulum (SR) was increased in the thyrotoxic muscles; this adaptation in the SR provides a possible mechanism for the alterations in isometric contractile properties. Thyrotoxicosis induced a large increase in fibers classified as type 2, on the basis of an alkali-stable histochemical reaction for ATPase, in the soleus. Although this reaction is commonly interpreted as indicating that a muscle is fast, maximum shortening velocity (Vmax) and Mg2+ activated actomyosin ATPase activity were unaffected in the thyrotoxic soleus. Our findings provide evidence that CT and Vmax can vary independently and that the histochemical ATPase reaction may not always reflect the biochemical properties that make myosin fast or slow.

Adenosine Triphosphatases↗

PubMed1980

Preferential resynthesis of muscle glycogen in fasting rats after exhausting exercise.

Despite carbohydrate starvation (fasting or fat feeding) considerable glycogen accumulation, ranging from 20 to 30 mumol glucose/g, occurred in hindlimb muscles of rats following exhausting exercise that caused severe muscle and liver glycogen depletion and hypoglycemia. The largest increase in muscle glycogen occurred during the first 3 h after exercise when plasma levels of glucagon and epinephrine were very high and insulin concentration was low. The concentrations of glycogen attained in different hindlimb muscles in the fasting and fat-fed animals were between 50 and 100% of the values found in rats fed carbohydrate after the exhausting exercise. In rats fed carbohydrate following exercise, liver glycogen accumulation greatly exceeds muscle glycogen accumulation. A remarkable difference in the response of liver glycogen was seen in the carbohydrate starved rats. In contrast to the rapid increase in muscle glycogen, liver glycogen was still essentially completely depleted in the fasting and fat-fed rats 24 h after exercise. This indicates that the glucose made available via gluconeogenesis was preferentialy channeled away from liver glycogen synthesis into muscle glycogen.

Animals↗

PubMed1979

Effect of training on hormonal responses to exercise in competitive swimmers.

The effects of 9 weeks of training on responses of plasma hormones to swimming were studied in eight competitive swimmers who had not trained for several months. Two types of swimming tests were used: (1) 200 yd, a high intensity, exhausting type of exercise in which maximal effort was required both before and after training, and (2) 1000 yd, a pace type of exercise in which subjects swam as fast as possible prior to training and at the same rate after training. Plasma levels of glucagon increased and of insulin decreased during 1000 yd of swimming, but were not altered by 200 yd of swimming. No training effects were apparent in responses of plasma insulin and glucagon to these shortterm, high intensity exercise tests. During the 1000 yd swim, plasma adrenaline was 0.8 ng/ml before vs. 0.1 ng/ml after training. Plasma noradrenaline response decreased from 3.4 to 1.2 ng/ml as a result of training. In the 200 yd swim, adrenaline, but not noradrenaline, was lower after training.

Adolescent↗

PubMed1979

Effect of endurance exercise training on plasma pancreatic polypeptide concentration during exercise.

The effect of exercise on human pancreatic polypeptide (hPP) levels was evaluated in five subjects preceding and following a conditioning program. During 90 min of exercise, the plasma concentration of hPP rose to a peak value five times higher than the resting level. After 2 mo of endurance exercise training, exercising at the same absolute work load resulted in only a twofold increase in hPP levels. Even at a higher work load, plasma hPP levels were significantly lower than the values observed prior to conditioning. These results show that plasma hPP concentrations rise during exercise and the magnitude of this response is significantly lower after 2 mo of endurance exercise training.

Adult↗

PubMed1979

Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria.

Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process.

Adenosine Triphosphate↗

PubMed1979

Induction of delta-aminolevulinic acid synthetase in muscle by exercise or thyroxine.

There is evidence that delta-aminolevulinic acid (ALA) synthetase is the rate-limiting enzyme in heme biosynthesis. Accumulation of the apoproteins of the mitochondrial cytochromes appears to be regulated by availability of heme. Exercise and thyrotoxicosis bring about increases in the cytochromes, and in other mitochondrial enzymes, in muscle. In this context, we have examined the effects of exercise and of thyroid hormones on ALA synthetase activity in skeletal muscle. Treadmill running and injection of thyroid hormones both resulted in significant increases in muscle ALA synthetase activity. A rise in ALA synthetase activity was evident within 17 h after a bout of vigorous exercise and 14 h after a single injection of thyroid hormones. The increase in ALA synthetase preceded the increase in cytochrome c, which was used as a mitochondrial marker. These results are compatible with the hypothesis that a relationship exists between heme synthesis and mitochondrial growth in which the rate-controlling step is ALA synthetase activity.

5-Aminolevulinate Synthetase↗

PubMed1979

Liver glycogenolysis during exercise without a significant increase in cAMP.

Liver glycogenolysis may be controlled by glucagon or catecholamine-induced changes in cAMP or by cAMP-independent mechanisms. The purpose of these experiments was to determine whether an increase in liver cAMP occurs during exercise at a time when the rate of liver glycogenolysis is greatly accelerated. Rats were taught to run on a treadmill 10 min/day for 6 wk. They were then run continuously for periods of time ranging from 0 to 120 min at 0.8 mph up a 15% grade. Liver glycogen was depleted by the end of 90 min in fed animals and by 20 min in overnight-fasted animals. Liver cAMP was not significantly increased in fed animals during the first 60 min of exercise. The major increase in liver cAMP occurred after liver glycogen was depleted, at which time the rat must rely entirely on gluconeogenesis for maintenance of blood glucose. This increase in cAMP corresponded to large increases in plasma glucagon and catecholamines. We conclude that liver glycogenolysis in the rat can occur during exercise independently from significant detectable increases in cAMP concentrations.

Animals↗