Biomedical subjects

W W Winder

Publications and source records attributed to W W Winder.

At least 19 recordsLinked to original sources

PubMed1992

Control of fructose 2,6-diphosphate in muscle of exercising fasted rats.

This study examined the role of epinephrine in controlling intramuscular signals that may accelerate lactate production in less active muscles during exercise. Sham-operated (sham) or adrenodemedullated (ADM) rats were fasted 24 h and then were killed at rest or after running for 15 or 30 min on a treadmill (21 m/min, 15% grade). One-half of the ADM rats were infused with epinephrine (6 micrograms/h) intravenously (jugular catheter) during exercise. ADM rats exhibited lower blood glucose, blood lactate, white quadriceps muscle content of lactate, glucose 6-phosphate, fructose 6-phosphate, and adenosine 3',5'-cyclic monophosphate (cAMP) during exercise than did sham rats or epinephrine-infused ADM rats. The white quadriceps muscle contents of fructose 2,6-diphosphate (F-2,6-P2) and glucose 1,6-diphosphate (G-1,6-P2) (allosteric activators of glycolysis) were at least two times as high in sham rats and in epinephrine-infused rats as in ADM rats during exercise. We conclude that the exercise-induced rise in epinephrine is responsible for the acceleration of glycolysis in less active muscle during exercise. This effect is likely mediated by epinephrine-induced increases in cAMP, F-2,6-P2, and G-1,6-P2.

Adrenal Medulla↗

PubMed1992

Nerve stimulation decreases malonyl-CoA in skeletal muscle.

This study was designed to determine the effect of in situ electrical stimulation of the sciatic nerve on malonyl-CoA, an inhibitor of carnitine palmitoyl transferase, in the gastrocnemius/plantaris muscle group of rats. The left sciatic nerve was stimulated at a frequency of 5 Hz with 100-ms trains of impulses (50 Hz) for 1, 3, or 5 min. At the end of stimulation, the left and right (nonstimulated) gastrocnemius/plantaris muscle groups were clamp-frozen and later analyzed for malonyl-CoA and other metabolites. No change was observed in the noncontracting contralateral muscles in malonyl-CoA, ATP, creatine phosphate (CP), or citrate. In the stimulated muscles, malonyl-CoA decreased from 1.7 +/- 0.1 to 1.0 +/- 0.1 nmol/g (P less than 0.05), and CP decreased from 15.8 +/- 0.9 to 12.2 +/- 1.0 mumol/g (P less than 0.05) after 3 min of stimulation. After 5 min of stimulation, malonyl-CoA was 1.0 +/- 0.1 nmol/g and CP was 10.3 +/- 1.3 mumol/g. When muscles were stimulated for 5 min with single impulses (5 Hz), malonyl-CoA was decreased from 1.8 +/- 0.3 to 1.0 +/- 0.1 nmol/g, with no change in CP, ATP, or adenosine 3',5'-cyclic monophosphate. Thus a decline in malonyl-CoA can be induced by muscle contraction independently of humoral influence.

Acetyl-CoA Carboxylase↗

PubMed1992

Insulin-induced hypoglycemia in fed and fasted exercising rats.

To determine running performance and hormonal and metabolic responses during insulin-induced hypoglycemia, fed and fasted male rats (315 +/- 3 g) were infused with insulin (100 mU/ml, 1.5 ml/h) or saline (1.5 ml/h) for 60 min and then killed at rest or after running on the treadmill (21 m/min, 15% grade). Insulin-infused fed rats ran poorly during the second 10 min of a 20-min exercise test. They were capable of running a total of 43 +/- 5 min, compared with 138 +/- 6 min for saline-infused fed rats. Fasted insulin-infused rats were able to run only 12.8 +/- 0.8 min, compared with 122 +/- 15 min for fasted saline-infused rats. In fasted rats, blood glucose was 1.6 +/- 0.1 mM after 60 min of insulin infusion and 1.2 +/- 0.1 mM after running to exhaustion. Artificial increase of plasma free fatty acids had no effect on performance. Intravenous infusion of glucose at the time of fatigue produced an immediate recovery, allowing the formerly fatigued rats to run 20 min without development of fatigue. These results provide evidence that severe hypoglycemia can be a significant cause of fatigue, even if it occurs early in the course of an exercise bout.

Animals↗

PubMed1991

Evidence of a biotin dependent acetyl-coenzyme A carboxylase in rat muscle.

Rat hindlimb muscle tissue was extracted from male Sprague-Dawley rats exsanguinated under light ether anesthesia. Muscle homogenates (50,000 x g supernatant) were incubated with ATP, bicarbonate, acetyl-CoA, and citrate. The quantity of malonyl-CoA synthesized was determined by malonyl-CoA incorporation into long acyl chains using tritiated acetyl-CoA and fatty acid synthetase. Malonyl-CoA synthesis was found to be dependent on the presence of ATP, bicarbonate, citrate, and acetyl-CoA in the incubation medium. Incubation with avidin showed near complete inhibition of carboxylation that was restored with the addition of biotin. These results represent strong evidence of a biotin containing acetyl-CoA carboxylase in skeletal muscle.

Acetyl-CoA Carboxylase↗

PubMed1991

Divergence of muscle and liver fructose 2,6-diphosphate in fasted exercising rats.

Previous studies demonstrate that nonexercising muscle may serve as a source of lactate for hepatic gluconeogenesis during long-term exercise. The concentration of fructose 2,6-diphosphate (F-2,6-P2), a signal molecule that accelerates glycolysis, was examined in liver and muscles of fed and fasted resting rats and in fasted rats run for 5, 15, or 30 min at 21 m/min (15% grade). Liver F-2,6-P2 decreased in response to fasting and exercise. White quadriceps (composed predominantly of type IIb fibers) F-2,6-P2 increased from 2.2 +/- 0.1 to 4.5 +/- 0.4 pmol/mg in the fasted rats in response to 30 min of treadmill running. No increase was observed in the red region of the quadriceps (composed of type IIa fibers). The fasted rats also exhibited a threefold increase in glucose 1,6-diphosphate (G-1,6-P2) in the white quadriceps after 30 min of exercise, whereas no significant changes were observed in the red quadriceps or in liver. The increases in F-2,6-P2 and G-1,6-P2 may be important in accelerating glycolysis and enhancing lactate production in muscles that are not glycogen depleted during long-term exercise.

Animals↗

PubMed1991

Effect of glucose infusion on muscle malonyl-CoA during exercise.

Previous work in this laboratory has shown that muscle malonyl-CoA, the inhibitor of carnitine palmitoyltransferase I (CPT I), decreased during exercise. Hepatic malonyl-CoA content decreases when glucose availability decreases such as during fasting or when the glucagon-to-insulin ratio increases such as during prolonged exercise or in response to insulin deficiency. To investigate the effect of glucose infusion on muscle malonyl-CoA during exercise, male rats were anesthetized (pentobarbital via venous catheters) at rest or after running (21 m/min, 15% grade) for 30 or 60 min. During exercise rats were infused with either glucose (0.625 g/ml) or saline at a rate of 1.5 ml/h. Gastrocnemius muscles and liver samples were frozen at liquid nitrogen temperature. Muscle malonyl-CoA decreased from 1.24 +/- 0.06 to 0.69 +/- 0.05 nmol/g with glucose infusion and to 0.43 +/- 0.04 nmol/g with saline infusion during 60 min of exercise. In the liver, glucose infusion prevented the drop in malonyl-CoA. This indicates that glucose infusion attenuates the progressive decline in muscle malonyl-CoA and prevents the decline in liver malonyl-CoA during prolonged exercise.

Animals↗

PubMed1991

Malonyl-CoA in skeletal muscle and liver of streptozotocin-diabetic rats.

Malonyl-CoA, the inhibitor of carnitine palmitoyl transferase I, has been examined in this study in the muscle and liver of diabetic rats. Male Sprague-Dawley rats were rendered diabetic with streptozotocin (6 mg/100 g body wt). The gastrocnemius/plantaris muscles and liver samples were frozen at liquid nitrogen temperature. Muscle malonyl-CoA was 1.8 +/- 0.2 pmol/mg in control rats and 1.5 +/- 0.2 pmol/mg in the diabetic rats. This difference was not statistically significant. Liver malonyl-CoA of control rats was 8.6 +/- 0.8 pmol/mg, in comparison to 4.3 +/- 0.6 pmol/mg in diabetic rats. In the liver, high concentrations of malonyl-CoA inhibit fatty acid oxidation and ketogenesis. Failure of malonyl-CoA to decline in muscle in the diabetic may be responsible in part for the diversion of fatty acids to the liver, thereby enhancing hepatic fatty acid oxidation and ketogenesis.

3-Hydroxybutyric Acid↗

PubMed1990

Glycogen repletion and exercise endurance in rats adapted to a high fat diet.

It is well accepted that exercise endurance is directly related to the amount of carbohydrate stored in muscle and that a low carbohydrate diet reduces glycogen storage and exercise performance. However, more recent evidence has shown that when the organism adapts to a high fat diet endurance is not hindered. The present study was designed to test that claim and to further determine if animals adapted to a high fat diet could recover from exhausting exercise and exercise again in spite of carbohydrate deprivation. Fat-adapted (3 to 4 weeks, 78% fat, 1% carbohydrates) rats (FAT) ran (28 m/min, 10% grade) as long as carbohydrate-fed (69% carbohydrates) animals (CHO) (115 v 109 minutes, respectively) in spite of lower pre-exercise glycogen levels in red vastus muscle (36 v 54 mumols/g) and liver (164 v 313 mumols/g) in the FAT group. Following 72 hours of recovery on the FAT diet, glycogen in muscle had replenished to 42 mumols/g (v 52 for CHO) and liver glycogen to 238 mumols/g (v 335 for CHO). The animals were run to exhaustion a second time and run times were again similar (122 v 132 minutes FAT v CHO). When diets were switched after run 1, FAT-adapted animals, which received carbohydrates for 72 hours, restored muscle and liver glycogen (48 and 343 mumols/g, respectively) and then ran longer (144 minutes) than CHO-adapted animals (104 minutes) that ate fat for 72 hours and that had reduced glycogen repletion. We conclude that, in contrast to the classic CHO loading studies in humans that involved acute (72 hours) fat feedings and subsequently reduced endurance, rats adapted to a high fat diet do not have a decrease in endurance capacity even after recovery from previous exhausting work bouts. Part of this adaptation may involve the increased storage and utilization of intramuscular triglycerides (TG) as observed in the present experiment.

Adaptation, Physiological↗

PubMed1990

Time course of exercise-induced decline in malonyl-CoA in different muscle types.

Malonyl-CoA is a potent inhibitor of carnitine palmitoyltransferase I (CPT-I), the rate-limiting enzyme for fatty acid oxidation in mitochondria from liver of fed rats. Malonyl-CoA has also been demonstrated to inhibit skeletal muscle CPT-I. This study was designed to determine the rate of decline in malonyl-CoA in muscle during the course of a prolonged exercise bout. Adult male rats were anesthetized (pentobarbital sodium, intravenously) at rest or after running for 5, 10, 20, 30, 60, or 120 min on a treadmill (21 m/min, 15% grade). Malonyl-CoA was then quantitated in the soleus (type I fibers) and in the superficial white (type IIB) and deep red (type IIA) regions of the quadriceps. Malonyl-CoA decreased in red quadriceps from 2.8 +/- 0.2 to 1.4 +/- 0.2 pmol/mg after 5 min and to 0.9 +/- 0.1 pmol/mg after 20 min of exercise. The concentration of malonyl-CoA remained at this level for the duration of the exercise bout (120 min). In white quadriceps, resting values of malonyl-CoA were lower than in red quadriceps, and a significant decline was not observed until 30 min of exercise. A significant decrease in the soleus was observed after 20 min of exercise. This decline in muscle malonyl-CoA may be an important signal for allowing increased fatty acid oxidation during long-term exercise.

Acyl Coenzyme A↗

PubMed1990

Effects of exercise on insulin-induced hypoglycemia.

The purpose of this study was to determine the effect of exercise on the rate of onset of hypoglycemia induced by infusion of excess insulin (0.8 mU.min-1.100 g-1). Rats were either fasted overnight (FS) or fed ad libitum (FD). FS rats were killed after 5, 10, or 15 min of infusion at rest or after running on the treadmill at 21 m/min and 15% grade. FD rats were killed after 10, 20, or 40 min of infusion at rest or after exercise. Rats were also killed 15 min postexercise for FS and 60 or 120 min postexercise for FD with continued insulin infusion. The progressive decline in blood glucose was not altered by exercise in the FS rats. FD rats showed a significant difference due to exercise only after 40 min (rest 4.2 +/- 0.3 mM, exercise 3.2 +/- 0.2 mM). A significant postexercise repletion of glycogen was observed in red vastus and soleus muscles of FD rats despite the decreasing blood glucose values. These data indicate that exercise accelerates the rate of development of hypoglycemia in FD rats. In the FS rats, where the rate of decline in blood glucose was greater, exercise had no effect on the time course of development of hypoglycemia.

Animals↗

PubMed1989

Effect of various doses of cocaine on endurance capacity in rats.

To determine the effects of a variety of doses of cocaine on endurance capacity, rats were injected intraperitoneally with either 0.1, 0.5, 2.5, 12.5, or 20 mg/kg body wt 20 min before running to exhaustion at 26 m/min up a 10% grade. Animals given saline ran 116 +/- 9 (SE) min. At doses of 12.5 and 20 mg/kg, cocaine reduced endurance time significantly (34 and 74%, respectively). At rest the drug had no effect on liver or fast-twitch muscle glycogen but significantly reduced (20-40%) soleus glycogen at the two highest doses. However, at exhaustion, the quantity of glycogen depleted in the fast-twitch red and white vastus muscles was similar in all groups despite the reduced run times of the animals receiving a higher dose implying a greater rate of glycogenolysis due to cocaine. Blood lactate in the 20 mg/kg group (9.9 +/- 1.2 mM) at exhaustion was nearly twice that of the saline controls at exhaustion (5.1 +/- 0.6). Before exercise plasma norepinephrine (at doses of 2.5, 12.5 and 20 mg/kg) was higher than saline controls and remained higher (20 mg/kg groups) at exhaustion. We conclude that high doses of cocaine cause rapid muscle glycogen depletion and early fatigue. The mechanism by which cocaine causes these effects is not clear.

Animals↗

PubMed1989

Muscle malonyl-CoA decreases during exercise.

Malonyl-CoA, the inhibitor of carnitine acyltransferase I, is an important regulator of fatty acid oxidation and ketogenesis in the liver. Muscle carnitine acyltransferase I has previously been reported to be more sensitive to malonyl-CoA inhibition than is liver carnitine acyltransferase I. Fluctuations in malonyl-CoA concentration may therefore be important in regulating the rate of fatty acid oxidation in muscle during exercise. Male rats were anesthetized (pentobarbital via venous catheters) at rest or after 30 min of treadmill exercise (21 m/min, 15% grade). The gastrocnemius/plantaris muscles were frozen at liquid N2 temperature. Muscle malonyl-CoA decreased from 1.66 +/- 0.17 to 0.60 +/- 0.05 nmol/g during the exercise. This change was accompanied by a 31% increase in cAMP in the muscle. The decline in malonyl-CoA occurred before muscle glycogen depletion and before onset of hypoglycemia. Plasma catecholamines, corticosterone, and free fatty acids were all significantly increased during the exercise. This exercise-induced decrease in malonyl-CoA may be important for allowing the increase in muscle fatty acid oxidation during exercise.

Acyl Coenzyme A↗

PubMed1989

Effect of intravenous caffeine on muscle glycogenolysis in fasted exercising rats.

Caffeine has been reported to enhance performance by increasing fat utilization and by sparing liver and muscle glycogen. The lipolytic effect of caffeine has been reported to be diminished in response to previous carbohydrate loading of the subjects. The present study was designed to investigate the effects of caffeine during submaximal exercise in rats where the influence of dietary carbohydrate was removed by fasting. Rats were fasted overnight and given injection of 25 mg.kg-1 caffeine (CAF) or 0.9% NaCl (SAL) 60 min before exercise. They were run for 15, 30, and 60 min on a rodent treadmill up a 15% grade at 21 m.min-1. Plasma free fatty acids (FFA) were significantly elevated to 0.72 +/- 0.04 mM in CAF as compared to 0.45 +/- 0.03 mM in SAL at the beginning of exercise. During exercise, however, a significant difference in FFA levels between CAF and SAL was seen only at 30 min and not at other time points. No significant decrease in muscle glycogenolysis was observed in the CAF as compared to SAL rats, and the liver cyclic AMP remained the same in both CAF and SAL. Blood lactate (mM) showed an increase due to caffeine only at 15 min of exercise (CAF = 2.4 +/- 0.2; SAL = 1.7 +/- 0.3). Intravenous caffeine during exercise did not alter plasma glucagon or blood glucose. We conclude that caffeine has no effect on muscle glycogen utilization in fasted rats during exercise even though there was an increased FFA in CAF rats at the beginning of exercise.

Animals↗

PubMed1989

Effect of caffeine on glycogenolysis during exercise in endurance trained rats.

Caffeine has been reported to enhance performance by increasing lipid oxidation and sparing liver and muscle glycogen in human subjects during prolonged endurance exercise. In the present study, the effects of intravenous caffeine on the liver and muscle glycogenolysis during exercise in endurance trained rats were investigated. Male endurance trained rats (2 h.d-1 for 6-7 wk) were given injections of 5 mg.kg-1 caffeine (5 CAF), 25 mg.kg-1 caffeine (25 CAF), or 0.9% sodium chloride (SAL) and were run on the treadmill for 45 min, 90 min, or until exhaustion at 26 m.min-1 up a 15% grade. Intravenous caffeine did not enhance the endurance run time: 5 CAF = 149 +/- 14 min, 25 CAF = 152 +/- 10 min, and SAL = 176 +/- 10 min. Caffeine did not influence the rate of liver glycogenolysis during exercise [liver glycogen (mmol glucose units.g-1) after 90 min: 5 CAF = 139 +/- 26, 25 CAF = 133 +/- 25, and SAL = 120 +/- 32]. Liver cAMP, muscle glycogen, plasma free fatty acids, blood glucose, and lactate were likewise not affected by caffeine [plasma free fatty acids (mM) after 90 min: 5 CAF = 0.42 +/- 0.04, 25 CAF = 0.45 +/- 0.07, and SAL = 0.41 +/- 0.05]. These data indicate that intravenous caffeine does not enhance the endurance run time or alter the plasma free fatty acids or liver and muscle glycogen utilization in endurance trained rats.

Animals↗

PubMed1988

Adrenodemedullation affects endurance but not hepatic fructose 2,6-bisphosphate.

Sham-operated (SHAM) and saline (ADM-S)- or epinephrine (ADM-E)-infused adrenodemedullated rats were run on a treadmill (21 m/min, 15% grade) for 80 min or until exhaustion. ADM-S rats had significantly lower endurance run times (116 +/- 6 min) than ADM-E rats (136 +/- 8 min) and SHAM rats (150 +/- 6 min). Liver glycogen content dropped from 56 +/- 4 to 10 +/- 2 mg/g in SHAM and from 54 +/- 4 to 18 +/- 5 mg/g in ADM-S and to 20 +/- 8 mg/g in ADM-E rats at 80 min. Liver glycogen was depleted in all rats at exhaustion. Liver fructose 2,6-bisphosphate was decreased markedly in exercising rats, and the extent of decrease was not influenced by adrenodemedullation or by epinephrine infusion. ADM-S rats showed impaired glycogen depletion in the white vastus lateralis and soleus muscles, hypoglycemia, and low blood lactate at 80 min and at exhaustion. Infusion of epinephrine into ADM rats reversed these deficiencies. These data indicate that the adrenal medulla is unessential for normal endurance exercise as long as liver glycogen is available. After liver glycogen is depleted, epinephrine from the adrenal medulla prevents hypoglycemia and is essential for allowing continuation of exercise.

Adrenal Medulla↗

PubMed1988

Liver fructose 2,6-bisphosphate in rats running at different treadmill speeds.

To determine the effect of work rate on liver fructose 2,6-bisphosphate (fructose 2,6-P2), rats were run for 5 min on a treadmill up a 15% grade at 16, 21, 26, 31, and 36 m/min. The liver content of fructose 2,6-P2 decreased 25, 42, 50, 62, and 71% from resting values after 5 min of running at these work rates. The time course of the decline in liver fructose 2,6-P2 was also studied in rats run at 16 m/min for times ranging from 5 to 100 min, at 23 m/min for times ranging from 5 to 60 min, and at 31 m/min for times of 5, 10, and 20 min. The hepatic content of fructose 2,6-P2 declined significantly after 5 min in all three groups of rats. The rate of decline was greatest in rats run at 31 m/min. After 100 min of running, fructose 2,6-P2 in livers of rats running at 16 m/min declined to levels seen in rats run at 31 m/min for 20 min. Changes in fructose 2,6-P2 occurred before a detectable decline in liver glycogen and in the absence of any significant change in blood glucose. Liver adenosine 3',5'-cyclic monophosphate (cAMP) was elevated after 5 min of exercise in rats running at 23 and 31 m/min but not in rats running at 16 m/min. By the end of exercise, hepatic cAMP was elevated in rats running at all speeds. The rapid decline in fructose 2,6-P2 probably plays a role in decreasing hepatic glycolysis, thereby ensuring that glucose 6-phosphate derived from glycogenolysis is diverted to blood glucose.

Animals↗

PubMed1988

Effects of glucose infusion in exercising rats.

To determine whether feedforward control of liver glycogenolysis during exercise is subject to negative feedback by elevated blood glucose, glucose was infused into exercising rats at a rate that elevated blood glucose greater than 10 mM. Liver glycogen content decreased 22.4 mg/g in saline-infused rats compared with 13.6 mg/g in glucose-infused rats during the first 40 min of treadmill running (21 m/min, 15% grade). Liver adenosine 3',5'-cyclic monophosphate (cAMP) concentration was significantly lower in the glucose-infused rats during the exercise bout. The concentration of hepatic fructose 2,6-bisphosphate remained elevated throughout the exercise bout in glucose-infused rats but decreased markedly in saline-infused rats. Plasma insulin concentration was higher and plasma glucagon concentration lower in glucose-infused rats than in saline-infused rats during exercise. Early in exercise, liver glycogenolysis proceeds in the glucose-infused rats despite the fact that glucose and insulin concentrations are markedly elevated and liver cAMP is unchanged from resting values. These observations suggest the existence of a cAMP-independent feedforward system for activation of liver glycogenolysis that can override classical negative feedback mechanisms during exercise.

Animals↗

PubMed1988

Effect of the exercise-induced increase in glucocorticoids on endurance in the rat.

To investigate the effect of the increase in glucocorticoids during exercise on endurance, rats were either sham operated (SO) or adrenalectomized. All adrenalectomized rats were given a subcutaneously implanted corticosterone pellet at the time of adrenalectomy. Adrenalectomized rats were injected with corticosterone (ADX Cort) or corn oil (ADX) 5 min before exercise. Rats were killed at rest or after running on a treadmill (21 m/min, 15% grade) until exhaustion. SO rats ran 138 +/- 6 min compared with 114 +/- 9 min for ADX Cort and 89 +/- 8 min for ADX. All differences in run times were significant (P less than 0.05). Corticosterone levels were similar in exhausted SO and ADX Cort groups. ADX exhausted rats had corticosterone levels similar to resting values in SO and ADX rats. Inhibition of the rise in glucocorticoids during exercise had no effect on liver glycogen, liver adenosine 3',5'-cyclic monophosphate, plasma insulin, blood glucose, lactate, glycerol, or 3-hydroxybutyrate, plasma norepinephrine, or red quadriceps and soleus glycogen. Plasma free fatty acids were significantly depressed at exhaustion in ADX rats compared with SO. These data show that glucocorticoids exert effects within the time frame of a prolonged exercise bout and play a role in increasing endurance.

Adrenalectomy↗