Activation by Exercise of Human Skeletal Muscle Pyruvate Dehydrogenase In Vivo

1982 ◽  
Vol 63 (1) ◽  
pp. 87-92 ◽  
Author(s):  
G. R. Ward ◽  
J. R. Sutton ◽  
N. L. Jones ◽  
C. J. Toews

1. The activity of pyruvate dehydrogenase in its active and inactive forms was measured in biopsy samples obtained from the vastus lateralis muscle of healthy subjects before and after exercise. 2. At rest, 40 ± 4% (mean ± sem) of the enzyme was in the active form. 3. After progressive aerobic exercise to exhaustion (n = 5), 88 ± 2·3% was in the active form. 4. After intermittent supramaximal short-term exercise (1 min exercise, 3 min rest) to exhaustion (n = 6), 60 ± 2·2% was in the active form. 5. After isometric maximal exercise of 65 ± 3·6 s duration (n = 3), only 39 ± 1% of the enzyme was in the active form. 6. Muscle glycogen depletion was greatest with intermittent exercise and least with isometric maximal exercise; in contrast, the increase in muscle lactate was least with progressive exercise (1·3 to 9·4 μmol/g), intermediate in intermittent maximal exercise (1·2 to 13·1 μmol/g) and greatest after isometric exercise (1·8 to 17·6 μmol/g). There were no significant differences between the three studies in the changes in lactate/pyruvate ratios. 7. In three subjects who exercised with one leg, activation of the enzyme was twice as great in the exercised as in the inactive leg. 8. The ratio of active to total enzyme in biopsies of resting muscle was greater in four well-trained athletes than in four untrained control subjects (70% compared with 41% respectively). 9. The activation of pyruvate dehydrogenase appears to play an important part in regulating the use of glycogen and glucose during exercise in man.

1995 ◽  
Vol 269 (3) ◽  
pp. E458-E468 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
L. C. Lands ◽  
T. M. Bragg ◽  
M. G. Hollidge-Horvat ◽  
...  

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.


1993 ◽  
Vol 75 (2) ◽  
pp. 712-719 ◽  
Author(s):  
G. C. Gaitanos ◽  
C. Williams ◽  
L. H. Boobis ◽  
S. Brooks

Eight male subjects volunteered to take part in this study. The exercise protocol consisted of ten 6-s maximal sprints with 30 s of recovery between each sprint on a cycle ergometer. Needle biopsy samples were taken from the vastus lateralis muscle before and after the first sprint and 10 s before and immediately after the tenth sprint. The energy required to sustain the high mean power output (MPO) that was generated over the first 6-s sprint (870.0 +/- 159.2 W) was provided by an equal contribution from phosphocreatine (PCr) degradation and anaerobic glycolysis. Indeed, within the first 6-s bout of maximal exercise PCr concentration had fallen by 57% and muscle lactate concentration had increased to 28.6 mmol/kg dry wt, confirming significant glycolytic activity. However, in the tenth sprint there was no change in muscle lactate concentration even though MPO was reduced only to 73% of that generated in the first sprint. This reduced glycogenolysis occurred despite the high plasma epinephrine concentration of 5.1 +/- 1.5 nmol/l after sprint 9. In face of a considerable reduction in the contribution of anaerobic glycogenolysis to ATP production, it was suggested that, during the last sprint, power output was supported by energy that was mainly derived from PCr degradation and an increased aerobic metabolism.


1982 ◽  
Vol 60 (5) ◽  
pp. 727-731 ◽  
Author(s):  
Michael E. Houston ◽  
Brian W. Farrance ◽  
Robyn I. Wight

The acute effects of two different frequencies of electrical stimulation on the metabolism of the vastus lateralis muscle were studied in young male and female adults. The quadriceps muscle group of one leg was stimulated for 60 min using surface electrodes that delivered square pulses of 0.6 ms duration, either continuously at 10 Hz (n = 5) or intermittently (n = 5) at 50 Hz (12 s stimulation, 48 s recovery). Biochemical analyses revealed no significant differences in glycogen or metabolite concentrations between the two conditions. Muscle lactate and citrate concentrations were increased (p < 0.05) for both conditions, but ATP and CP concentrations were not significantly changed from rest values after stimulation. Glycogen concentrations decreased (p < 0.05) by 24.6 and 29.1 mmol glucose units/kg after 60 min of 50 Hz and 10 Hz stimulation, respectively. Muscle fibres were identified as slow twitch (ST) and fast twitch a and b (FTa and FTb) on the basis of myofibrillar ATPase activity. Estimates of glycogen depletion in different fibre types using histochemical techniques revealed that FTa and FTb fibres had lower glycogen contents than ST fibres after 10 Hz stimulation whereas glycogen was moderately reduced in approximately 50% of all fibre types following 50 Hz stimulation. The modest changes observed in muscle metabolism following 60 min of stimulation were less than has been noted following traditional exercise, and suggest that only some of the muscle fibres were activated in the stimulated muscles at the depth where biopsy samples were removed.


2002 ◽  
Vol 282 (1) ◽  
pp. R273-R280 ◽  
Author(s):  
Jens Bangsbo ◽  
Martin J. Gibala ◽  
Peter Krustrup ◽  
José González-Alonso ◽  
Bengt Saltin

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDHa) and, subsequently, measured leg O2uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at ∼110% of thigh peak O2uptake (65.3 ± 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2uptake and lactate release. After DCA administration, PDHawas four- to eightfold higher ( P < 0.05) than Con at rest, and PDHaremained ∼130% and 100% higher ( P< 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDHabetween trials at rest and during the initial phase of exercise, thigh O2uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDHadoes not alter muscle O2uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.


1999 ◽  
Vol 87 (3) ◽  
pp. 1083-1086 ◽  
Author(s):  
G. McConell ◽  
R. J. Snow ◽  
J. Proietto ◽  
M. Hargreaves

Eight endurance-trained men cycled to volitional exhaustion at 69 ± 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies ( n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by ∼30% when carbohydrate was ingested [199 ± 21 vs. 152 ± 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 ± 0.08, Con: 0.23 ± 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.


1978 ◽  
Vol 45 (6) ◽  
pp. 852-857 ◽  
Author(s):  
P. D. Gollnick ◽  
J. Karlsson ◽  
K. Piehl ◽  
B. Saltin

Experiments were conducted to examine the conversions of phosphorylase b to phosphorylase a in human skeletal muscle during bicycle exercise or isometric contractions. Muscle biopsies were obtained from the vastus lateralis with the needle technique at rest and either during or immediately after activity and frozen in liquid nitrogen within 2--4 s. Total phosphorylase and phosphorylase a activities were differentiated by measurement in the presence and absence of AMP, respectively. At rest 8.5% of the total phosphorylase activity existed in the a form. Little or no change in the percent of phosphorylase in the a form occurred during voluntary dynamic or static muscular activity that produced muscle lactate concentrations in excess of 18 mmol.kg-1 wet muscle. Electrical stimulation of the vastus lateralis muscle also failed to produce an increase in the percentage of phosphorylase a. These data suggest that during exercise the conversion of phosphorylase to the a form is of minor importance. An increased activity of phosphorylase b due to changes in muscle concentrations of ATP, AMP, and inorganic phosphate may regulate glycogenolysis during voluntary exercise in man.


1987 ◽  
Vol 63 (3) ◽  
pp. 1107-1113 ◽  
Author(s):  
G. A. Fantini ◽  
J. P. Roberts ◽  
S. F. Lowry ◽  
J. D. Albert ◽  
K. J. Tracey ◽  
...  

Hormonal and substrate influences on in vivo cellular membrane function were evaluated in 15 healthy male volunteers. Each subject underwent serial evaluations of membrane function in the anterior tibialis muscle, as assessed by transcutaneous measurement of resting membrane potential (Em). Group A subjects (n = 9) underwent measurement of resting Em in the basal state and again during the 10th day of intravenous feeding (IVF). Group B subjects (n = 6) underwent measurement of resting Em in the basal state during epinephrine infusion and again during epinephrine infusion on the 7th day of IVF. Percutaneous needle biopsy of the vastus lateralis muscle permitted calculation of transmembrane electrolyte distribution from the Nernst equation, using the measured Em and the chloride space method. Hospitalization with intake of a defined-formula enteral diet for 3 days resulted in depolarization (P less than 0.05) of resting Em (-75.3 +/- 1.6 mV) compared with normal (-79.8 +/- 0.9 mV). Despite 10 days of subsequent IVF, further depolarization (P less than 0.05) of resting Em (-71.2 +/- 1.2 mV) was observed. In the dual presence of IVF and exogenous epinephrine infusion, there was an increase (P less than 0.05) in intracellular potassium concentration and repolarization of resting Em (-80.6 +/- 0.8 mV) to normal levels. These data indicate that hormonal background and substrate availability contribute to the in vivo modulation of cellular membrane function in human skeletal muscle, possibly through facilitation of sodium-dependent amino acid transport across the cell membrane.


1993 ◽  
Vol 75 (4) ◽  
pp. 1502-1506 ◽  
Author(s):  
T. P. Rooney ◽  
Z. V. Kendrick ◽  
J. Carlson ◽  
G. S. Ellis ◽  
B. Matakevich ◽  
...  

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.01 ml of sunflower oil-1 x 100 g body wt-1) on the temporal pattern of exercise-induced tissue glycogen depletion and tissue lipid availability during submaximal treadmill running was determined in male rats. Animal were administered estradiol or oil for 5 days and were then time matched for motorized treadmill running for 30, 60, 90, or 120 min. Significant depletion of liver, soleus muscle, and red and white vastus lateralis muscle tissue glycogen occurred in oil-administered animals run between 30 and 120 min. The greatest extent of tissue glycogen depletion occurred during the first 30 min of exercise with the rate of glycogen depletion slowing between 30 and 120 min of exercise. Administration of estradiol attenuated the temporal pattern of glycogen depletion in both liver and muscle tissues. Significant depletion of red and white vastus glycogen of estradiol-administered animals did not occur until 90 and 120 min of exercise, respectively. Administration of estradiol significantly increased resting plasma free fatty acids and red and white vastus triacylglycerol content. These data indicate that estradiol administration for 5 days resulted in significant glycogen sparing of liver and muscle tissues during submaximal treadmill running for up to 120 min by altering the temporal pattern of glycogen depletion of male rats secondary to an estradiol-mediated increase in availability of lipid substrate during exercise.


2000 ◽  
Vol 88 (3) ◽  
pp. 851-856 ◽  
Author(s):  
Y. Ichinose ◽  
Y. Kawakami ◽  
M. Ito ◽  
H. Kanehisa ◽  
T. Fukunaga

To determine the shortening velocities of fascicles of the vastus lateralis muscle (VL) during isokinetic knee extension, six male subjects were requested to extend the knee with maximal effort at angular velocities of 30 and 150°/s. By using an ultrasonic apparatus, longitudinal images of the VL were produced every 30 ms during knee extension, and the fascicle length and angle of pennation were obtained from these images. The shortening fascicle length with extension of the knee (from 98 to 13° of knee angle; full extension = 0°) was greater (43 mm) at 30°/s than at 150°/s (35 mm). Even when the angular velocity remained constant during the isokinetic range of motion, the fascicle velocity was found to change from 39 to 77 mm/s at 150°/s and from 6 to 19 mm/s at 30°/s. The force exerted by a fascicle changed with the length of the fascicle at changing angular velocities. The peak values of fascicle force and velocity were observed at ∼90 mm of fascicle length. In conclusion, even if the angular velocity of knee extension is kept constant, the shortening velocity of a fascicle is dependent on the force applied to the muscle-tendon complex, and the phenomenon is considered to be caused mainly by the elongation of the elastic element (tendinous tissue).


2004 ◽  
Vol 286 (3) ◽  
pp. E488-E494 ◽  
Author(s):  
C. B. Djurhuus ◽  
C. H. Gravholt ◽  
S. Nielsen ◽  
S. B. Pedersen ◽  
N. Møller ◽  
...  

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 μg·kg-1·min-1hydrocortisone infusion (II), a 200-μg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 ± 0.08 μg/l, mean ± SE). Peak levels during III and IV were ∼9 μg/l. Cortisol levels rose to ∼900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.


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