Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate

The purpose of this study was to determine whether the postponement of fatigue in subjects fed carbohydrate during prolonged strenuous exercise is associated with a slowing of muscle glycogen depletion. Seven endurance-trained cyclists exercised at 71 +/- 1% of maximal O2 consumption (VO2max), to fatigue, while ingesting a flavored water solution (i.e., placebo) during one trial and while ingesting a glucose polymer solution (i.e., 2.0 g/kg at 20 min and 0.4 g/kg every 20 min thereafter) during another trial. Fatigue during the placebo trial occurred after 3.02 +/- 0.19 h of exercise and was preceded by a decline (P less than 0.01) in plasma glucose to 2.5 +/- 0.5 mM and by a decline in the respiratory exchange ratio (i.e., R; from 0.85 to 0.80; P less than 0.05). Glycogen within the vastus lateralis muscle declined at an average rate of 51.5 +/- 5.4 mmol glucosyl units (GU) X kg-1 X h-1 during the first 2 h of exercise and at a slower rate (P less than 0.01) of 23.0 +/- 14.3 mmol GU X kg-1 X h-1 during the third and final hour. When fed carbohydrate, which maintained plasma glucose concentration (4.2-5.2 mM), the subjects exercised for an additional hour before fatiguing (4.02 +/- 0.33 h; P less than 0.01) and maintained their initial R (i.e., 0.86) and rate of carbohydrate oxidation throughout exercise. The pattern of muscle glycogen utilization, however, was not different during the first 3 h of exercise with the placebo or the carbohydrate feedings. The additional hour of exercise performed when fed carbohydrate was accomplished with little reliance on muscle glycogen (i.e., 5 mmol GU X kg-1 X h-1; NS) and without compromising carbohydrate oxidation. We conclude that when they are fed carbohydrate, highly trained endurance athletes are capable of oxidizing carbohydrate at relatively high rates from sources other than muscle glycogen during the latter stages of prolonged strenuous exercise and that this postpones fatigue.     

Effects of gluconeogenic precursor flux alterations on glycogen resynthesis after prolonged exercise

The importance of gluconeogenic substrates (i.e., lactate, glycerol, and alanine) in the glycogen resynthesis observed in fasting rats after exhausting submaximal exercise [R.D. Fell et al. Am. J. Physiol. 238 (Regulatory Integrative Comp. Physiol. 7): R328-R332, 1980] was examined in muscles and liver in response to pharmacological alterations of gluconeogenic precursor flux. The minor role of lactate for glycogen resynthesis after prolonged submaximal exercise was confirmed by the insignificant accumulation of lactate neither in muscles nor in plasma. When the rate of lipolysis is reduced either by beta-blockade or by nicotinic acid injection, the replenishment of muscle glycogen persisted, suggesting that glycerol released by triglycerides hydrolysis did not play an important role in glycogen resynthesis. On the other hand, when pyruvate oxidation is enhanced by dichloroacetate (DCA), thus reducing plasma levels of lactate and alanine, glycogen resynthesis was completely blocked in liver and partly in some but not all muscles. This failure in total inhibition of glycogen resynthesis associated with the significant reduction of the plasma alanine level could be attributed to the possible stimulation of gluconeogenesis from alanine by DCA (R.A. Harris and D.W. Crabb. Arch. Biochem. Biophys. 189: 364-371, 1978). The results could point out alanine as the major gluconeogenic substrate during recovery from exhaustive exercise in fasting conditions.     

Training decreases muscle glycogen turnover during exercise

The present study was undertaken to determine the effects of endurance training on glycogen kinetics during exercise. A new model describing glycogen kinetics was applied to quantitate the rates of synthesis and degradation of glycogen. Trained and untrained rats were infused with a 25% glucose solution with 6-³H-glucose and U-¹⁴C-lactate at 1.5 and 0.5 μCi · min⁻¹ (where 1 Ci = 3.7 × 10¹⁰ Bq), respectively, during rest (30 min) and exercise (60 min). Blood samples were taken at 10-min intervals starting just prior to isotopic infusion, until the cessation of exercise. Tissues harvested after the cessation of exercise were muscle (soleus, deep, and superficial vastus lateralis, gastrocnemius), liver, and heart. Tissue glycogen was quantitated and analyzed for incorporation of ³H and ¹⁴C via liquid scintillation counting. There were no net decreases in muscle glycogen concentration from trained rats, whereas muscle glycogen concentration decreased to as much as 64% (P < 0.05) in soleus in muscles from untrained rats after exercise. Liver glycogen decreased in both trained (30%) and untrained (40%) rats. Glycogen specific activity increased in all tissues after exercise indicating isotope incorporation and, thus, glycogen synthesis during exercise. There were no differences in muscle glycogen synthesis rates between trained and untrained rats after exercise. However, training decreased muscle glycogen degradation rates in total muscle (i.e., the sum of the degradation rates of all of the muscles sampled) tenfold (P < 0.05). We have applied a model to describe glycogen kinetics in relation to glucose and lactate metabolism during exercise in trained and untrained rats. Training significantly decreases muscle glycogen degradation rates during exercise. Accepted: 22 May 1998     

How important is endogenous muscle glycogen to fatigue in prolonged exercise?

Endogenous muscle glycogen represents a primary fuel source during large muscle group activity in the human. The depletion of this fuel source during submaximal exercise at intensities ranging between 60 and 85% of maximal aerobic power (Vo2max) is widely believed to be the cause of an inability to sustain exercise. Alterations of preexercise muscle glycogen reserves by dietary and exercise manipulations and changing the degree of dependency on endogenous glycogen during exercise by modifying the availability of other fuel sources have in general served to establish a close relationship between muscle glycogen and fatigue resistance. However, in spite of the evidence implicating glycogen depletion to fatigue, the mechanism remains elusive. The most popular theory is that glycogen is an essential substrate, the depletion of which results in a reduction in the rate of ATP regeneration and an inability to maintain energy supply to one or more of the processes involved in excitation and contraction in the muscle. As a consequence, the muscle is unable to translate the motor drive into an expected force and fatigue develops. However, there is little experimental evidence to support this theory. Most studies report no or only minimal changes in ATP concentration at fatigue with low glycogen and no further change in the by-products of ATP hydrolysis. These findings suggest that fatigue might be caused by other nonmetabolic factors. This review examines these other nonmetabolic factors and analyzes their potential role in fatigue during prolonged exercise with depletion of muscle glycogen reserves.     

Implementation of periodic acid-thiosemicarbazide-silver proteinate staining for ultrastructural assessment of muscle glycogen utilization during exercise

Summary Distribution of glycogen particles in semithin and ultrathin sections of biopsy samples from human muscles subjected to either short- or long-term running were investigated using PAS and Periodic Acid-ThioSemiCarbazide-Silver Proteinate (PA-TSC-SP) staining methods. Glycogen particles were predominantly found immediately under the sarcolemma or aligned along the myofibrillar Iband. After long-term exhaustive exercise type-1 fibers with a few or no glycogen particles in the core of the fibers were frequently observed. The subsarcolemmal glycogen stores of these depleted type-1 fibers were about three times as large as after exhaustive short-time exercise. Another indication of utilization of subsarcolemmal glycogen stores during anaerobic exercise was that many particles displayed a pale, rudimentary shape. This observation suggests fragmental metabolization of glycogen. Thus, depending on type of exercise and type of fiber differential and sequential glycogen utilization patterns can be observed.     

Training-induced alterations in young and senescent rat diaphragm muscle.

The current study sought to examine the effects of chronic endurance treadmill running on oxidative capacity and capillary density in specific diaphragm muscle fiber types in young (5 mo) and senescent (greater than or equal to 23 mo) female Fischer 344 rats. Both young and senescent animals trained at approximately 75% of maximal O2 consumption for 1 h/day 5 days/wk for 10 wk. Plantaris citrate synthase activity was significantly increased (P less than 0.01) in both young and old trained groups. Densitometric analysis of succinate dehydrogenase (SDH) activity in diaphragm type I, IIa, and IIb muscle fibers was done using a computerized image-processing system. There were no age-related differences in SDH activity between the young and old groups for any of the fiber types. In addition, SDH activity was found to be significantly increased (P less than 0.05) in all three fiber types in both the young and senescent trained animals compared with their sedentary counterparts. Fiber size and capillary density did not differ between young and senescent rats, nor did exercise affect this measure. Each fiber, irrespective of type, had an average of approximately four capillaries in contact with it. However, type IIb fibers had a significantly lower capillary density per unit area than type I or IIa muscle fibers. The results indicate that the senescent costal diaphragm maintains its ability to adapt to an increased metabolic demand brought about by locomotor exercise. Of further interest is the finding that training adaptations occurred in all three fiber types, suggesting that increased work of breathing from moderate exercise leads to recruitment of all three fiber types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Menstrual cycle phase and sex influence muscle glycogen utilization and glucose turnover during moderate-intensity endurance exercise

Numerous studies from our and other laboratories have shown that women have a lower respiratory exchange ratio (RER) during exercise than equally trained men, indicating a greater reliance on fat oxidation. Differences in estrogen concentration between men and women likely play a role in this sex difference. Differing estrogen and progesterone concentrations during the follicular (FP) and luteal (LP) phases of the female menstrual cycle suggest that fuel use may also vary between phases. The purpose of the current study was to determine the effect of menstrual cycle phase and sex upon glucose turnover and muscle glycogen utilization during endurance exercise. Healthy, recreationally active young women (n = 13) and men (n = 11) underwent a primed constant infusion of [6,6-2H]glucose with muscle biopsies taken before and after a 90-min cycling bout at 65% peak O2 consumption. LP women had lower glucose rate of appearance (Ra, P = 0.03), rate of disappearance (Rd, P = 0.03), and metabolic clearance rate (MCR, P = 0.04) at 90 min of exercise and lower proglycogen (P = 0.04), macroglycogen (P = 0.04), and total glycogen (P = 0.02) utilization during exercise compared with FP women. Men had a higher RER (P = 0.02), glucose Ra (P = 0.03), Rd (P = 0.03), and MCR (P = 0.01) during exercise compared with FP women, and men had a higher RER at 75 and 90 min of exercise (P = 0.04), glucose Ra (P = 0.01), Rd (P = 0.01), and MCR (P = 0.001) and a greater PG utilization (P = 0.05) compared with LP women. We conclude that sex, and to a lesser extent menstrual cycle, influence glucose turnover and glycogen utilization during moderate-intensity endurance exercise.     

Thermoregulation during prolonged exercise in heat: alterations with beta-adrenergic blockade

Thermoregulation and cardiovascular drift were studied under conditions of prolonged exercise in a warm environment (dry bulb temperature 31.7 +/- 0.3 degrees C, rh 44.7 +/- 4.7%) during beta-adrenergic blockade. Fourteen subjects performed 90-min rides on a cycle ergometer at a work rate equivalent to 40% of their control maximal O2 uptake under each of three treatments provided in a randomized double-blind manner: atenolol (100 mg/day), propranolol (160 mg/day), and a placebo. Exercise during the propranolol trial resulted in significantly higher forearm vascular resistance values and significantly lower forearm blood flows (FBF) compared with the placebo trial. However, the significantly lower FBF during propranolol did not significantly alter the rectal temperature (Tre) response to prolonged exercise. In addition, both beta-blockers produced lower FBF for any given Tre, suggesting that beta-adrenergic blockade affects FBF through nonthermal factors. The slight differences in Tre, despite the large differences in FBF between the various treatments, are apparently the result of an enhanced sweat loss and a lower mean skin temperature during exercise with beta-blockade. The uncoupling of FBF and sweat loss provides evidence of independent regulation. The reduction in FBF at any given Tre was concomitant to lower blood pressure values during beta-blockade and suggests that baroreflexes provide significant input to the control of skin blood flow when both pressure and temperature maintenance are simultaneously challenged.     

Fiber type specific glycogen utilization in rat diaphragm during treadmill exercise

To examine the significance of endogenous stores of glycogen in specific fiber types (I, IIa, IIb) of the costal region of the diaphragm, adult male Wistar rats performed continuous running (25 m/min, 8 degrees grade) exercise for either 30 min or until fatigue. At 30 min of exercise, glycogen loss, as measured microphotometrically using the periodic acid-Schiff technique averaged between 73 and 80% (P less than 0.05) in the different fiber types. When exercise was performed to exhaustion, representing an additional 94 min, no further reduction in glycogen was observed in any fiber type. Biochemical determinations of glycogen from the diaphragm confirmed the extensive reduction in glycogen concentration with exercise. Large reductions (P less than 0.05) in glycogen were also noted in the soleus, plantaris, and vastus lateralis red. Although significant depletion (P less than 0.05) occurred in the vastus lateralis white, it was not as pronounced as in these other muscles. Repletion to preexercise glycogen concentration was complete by 4 h of recovery in all muscles except the vastus lateralis white. It is concluded that endogenous glycogen is a significant substrate in all muscles sampled regardless of fiber composition. In the case of the costal region of the diaphragm, the increased work of breathing resulting from heavy exercise leads to the recruitment of all fiber types, and each fiber type depends on glycogen as a substrate at least early in the exercise.     

Hyperammoniemia during prolonged exercise: an effect of glycogen depletion?

Eight healthy men exercised to exhaustion on a cycle ergometer at a work load of 176 +/- 9 (SE) W corresponding to 67% (range 63-69%) of their maximal O2 uptake (exercise I). Exercise of the same work load was repeated after 75 min of recovery (exercise II). Exercise duration (range) was 65 (50-90) and 21 (14-30) min for exercise I and II, respectively. Femoral venous blood samples were obtained before and during exercise and analyzed for NH3 and lactate. Plasma NH3 was 12 +/- 2 and 19 +/- 6 mumol/l before exercise I and II, respectively and increased during exercise to exhaustion to peak values of 195 +/- 29 (exercise I) and 250 +/- 30 (exercise II) mumol/l, respectively. Plasma NH3 increased faster during exercise II compared with exercise I and at the end of exercise II was threefold higher than the value for the corresponding time of exercise I (P less than 0.001). Blood lactate increased during exercise I and after 20 min of exercise was 3.7 +/- 0.4 mmol/l and remained unchanged until exhaustion. During exercise II blood lactate increased less than during exercise I. It is concluded that long-term exercise to exhaustion results in large increases in plasma NH3 despite relatively low levels of blood lactate. It is suggested that the faster increase in plasma NH3 during exercise II (vs. exercise I) reflects an increased formation in the working muscle that may be caused by low glycogen levels and impairment of the ATP resynthesis.     

Muscle glycogen oxidation during prolonged exercise measured with oral [13C]glucose: comparison with changes in muscle glycogen content.

Plasma glucose and muscle glycogen oxidation during prolonged exercise [75-min at 48 and 76% maximal O(2) uptake (Vo(2 max))] were measured in eight well-trained male subjects [Vo(2 max) = 4.50 l/min (SD 0.63)] using a simplified tracer technique in which a small amount of glucose highly enriched in (13)C was ingested: plasma glucose oxidation was computed from (13)C/(12)C in plasma glucose (which was stable beginning at minute 30 and minute 15 during exercise at 48 and 76% Vo(2 max), respectively) and (13)CO(2) production, and muscle glycogen oxidation was estimated by subtracting plasma glucose oxidation from total carbohydrate oxidation. Consistent data from the literature suggest that this small dose of exogenous glucose does not modify muscle glycogen oxidation and has little effect, if any, on plasma glucose oxidation. The percent contributions of plasma glucose and muscle glycogen oxidation to the energy yield at 48% Vo(2 max) [15.1% (SD 3.8) and 45.9% (SD 5.8)] and at 76% Vo(2 max) [15.4% (SD 3.6) and 59.8% (SD 9.2)] were well in line with data previously reported for similar work loads and exercise durations using conventional tracer techniques. The significant reduction in glycogen concentration measured from pre- and postexercise vastus lateralis muscle biopsies paralleled muscle glycogen oxidation calculated using the tracer technique and was larger at 76% than at 48% Vo(2 max). However, the correlation coefficients between these two estimates of muscle glycogen utilization were not different from zero at each of the two work loads. The simplified tracer technique used in the present experiment appears to be a valid alternative approach to the traditional tracer techniques for computing plasma glucose and muscle glycogen oxidation during prolonged exercise.     

13C-NMR measurements of muscle glycogen during low-intensity exercise

Glycogen metabolism in exercising gastrocnemius muscles was examined by natural abundance 13C nuclear magnetic resonance (NMR) spectroscopy. Five-minute 13C-NMR measurement of muscle glycogen had a reproducibility of +/- 6.5% (+/- 4.8 mM). Experiments were performed on healthy fed male and female subjects. Two protocols were followed. 1) Subjects performed plantar flexion from rest at 15, 20, or 25% of maximum voluntary contraction for up to 9 h. 2) Subjects predepleted gastrocnemius glycogen with heavy exercise and then either performed low-intensity exercise as before or rested. Gastrocnemius glycogen was measured by NMR at rest and after each hour of exercise. In some sessions, both the exercised leg and the nonexercised leg were monitored with 13C-NMR. In protocol 1, blood velocity in the femoral artery was similarly assessed with ultrasonography. During low-intensity exercise from rest (protocol 1) muscle glycogen fell to a new steady-state value after several hours and then remained constant despite continued exercise. Mean blood velocity increased ninefold within 2 min of onset of exercise and remained constant thereafter. After predepletion (protocol 2), muscle glycogen was repleted both during low-intensity exercise and at rest. After 1 h the amount of glycogen repletion was greater when coupled with light exercise [48.5 +/- 2.8 mM after 1 h of exercise, 39.7 +/- 1.1 mM after 1 h of rest (P less than 0.05)]. During subsequent light exercise, glycogen reached a steady-state value similar to that obtained in protocol 1, while in resting, recovery glycogen levels continued to increase (+2.7 mM/h) over a 7-h period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenine nucleotide degradation in human skeletal muscle during prolonged exercise

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5'-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.     

Progressive elevations in muscle blood flow during prolonged exercise in swine

Distribution of muscle blood flow has not been measured in man during prolonged exercise, but progressive elevations in skin flow coupled with constant cardiac output (QT) have suggested muscle blood flow may be compromised. However, previous experiments with rats demonstrated progressive increases in muscle blood flow over time during prolonged submaximal exercise. The present study was performed to study muscle blood flow in miniature swine during long-term exercise to shed light on this apparent anomaly. QT and distribution of QT were studied with radiolabeled microspheres while pigs ran on a level treadmill at a speed (10.5 km/h) requiring 71 +/- 4% of maximal O2 consumption (VO2 max). QT increased 23% from the 5th to the 30th min of exercise, whereas total skeletal muscle flow increased by 49%. Increases in flow in the muscles resulted from decreased resistance, since mean arterial pressure declined over this time period (-7%). In addition, the proportional increases in muscle flow were similar within synergistic muscle groups independent of fiber type composition (e.g., elbow extensors: 59-78%; elbow flexors: 26-40%). The factor that limited continued exercise appeared to be body temperature. Colonic temperature rose in linear fashion over time; the animals became exhausted at approximately 42 degrees C. These flow data are similar to previous findings in rats and indicate that during prolonged treadmill locomotion in quadrupedal animals muscle blood flow increases over time to near maximal levels.     

Plateau in muscle blood flow during prolonged exercise in miniature swine

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8-10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210-220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.