Pathway of free fatty acid oxidation in human subjects. Implications for tracer studies.

To determine the pathway of plasma FFA oxidation and the site(s) of label fixation observed during infusion of FFA tracers, [1-13C]palmitate and [1-14C]acetate were infused intravenously for 3 h in five volunteers. Breath 13CO2 enrichment and 14CO2 specific activity were followed for 6 h to determine the labeled CO2 decay rates. Acetate enters directly into the TCA cycle; hence, if palmitate transits a large lipid pool before oxidation, 13CO2 enrichment (from palmitate) should decay slower than 14CO2 specific activity (from acetate). Breath 13CO2 enrichment and 14CO2 specific activity decayed at a similar rate after stopping the tracer infusions (half-lives of 13CO2 and 14CO2 decay: mean [+/- SE] 106.6 +/- 8.9 min, and 96.9 +/- 6.0 min, respectively, P = NS), which suggests that palmitate enters the TCA cycle directly and that label fixation occurs after citrate synthesis. Significant label fixation was shown in plasma glutamate/glutamine and lactate/pyruvate during infusion of either [1,2-13C]acetate or [U-13C]palmitate, suggesting that TCA cycle exchange reactions are at least partly responsible for label fixation. This was consistent with our finding that the half-lives of 13CO2 enrichment and 14CO2 specific activity decreased significantly during exercise to 14.4 +/- 3 min and 16.8 +/- 1 min, respectively, since exercise significantly increases the rate of the TCA cycle in relation to that of the TCA cycle exchange reactions. We conclude that plasma FFA entering cells destined to be oxidized are directly oxidized and that tracer estimates of plasma FFA oxidation will underestimate the true value unless account is taken of the extent of label fixation.

Lipid and carbohydrate metabolism in IDDM during moderate and intense exercise.

Insulin-dependent diabetes mellitus (IDDM) is characterized by a metabolic and hormonal disarray that may be more evident during exercise. However, the metabolic response to exercise of different intensities has not been evaluated in IDDM. We therefore used stable isotope techniques and indirect calorimetry to quantify substrate kinetics and oxidation during 30 min of exercise at 45 and 75% of maximal oxygen uptake (Vo2max) in seven men with IDDM (D group) infused with insulin at a constant basal rate. Normal control subjects (C group) matched for age, weight, and Vo2max were also studied. During moderate exercise, glucose uptake (Rd) was lower in the D than in the C group (15.3 +/- 1.0 vs. 20.8 +/- 1.6 mumol.min-1.kg-1; P < 0.05). Carbohydrate oxidation also tended to be lower in the D group (71.0 +/- 7.2 vs. 87.5 +/- 10.6 mumol.min-1.kg-1; P = 0.08). The D group relied on fat oxidation to a greater extent than did the C group (16.9 +/- 1.1 vs. 10.4 +/- 1.6 mumol.min-1.kg-1; P < 0.05). The enhanced fat oxidation was not due to increased lipolysis because no differences occurred in glycerol release (Ra) or in plasma free fatty acid Ra or concentration, and the source of the extra lipid appeared to be intramuscular fat stores. These differences in substrate metabolism were not evident during exercise at 75% of Vo2max. The lower glucose uptake and oxidation in the diabetic subjects during moderate, but not intense, exercise suggest that glucose metabolism is regulated differently depending on exercise intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle biopsy as a tool in the study of aging.

The needle biopsy procedure provides a minimally invasive means of obtaining small samples of skeletal muscle from human volunteers. Such samples can be used to examine a variety of structural and functional characteristics of muscle, including fiber type and size, capillarization, enzymatic capacities, energy substrate or protein/mRNA concentrations, metabolic responses, and contractile properties. In conjunction with other methods, biopsy sampling can also be used to estimate total muscle mass and fiber number, and to determine rates of protein synthesis and degradation. Optimal handling and storage conditions vary widely, but in general, most of the above measurements can be made using frozen tissue, so that samples can be stored almost indefinitely. The procedure is also safe and generally well-tolerated, making it possible to perform longitudinal studies of the same person. The biopsy technique is therefore well suited for examining the underlying physiological mechanisms responsible for muscle wasting in the elderly, as well as for assessing the effects of nutritional, hormonal, and/or lifestyle (e.g., exercise) interventions intended to combat this problem. Although sample size limitations have been largely overcome by the development of microtechniques, more information is needed on how to minimize the variability introduced by studying only a small fraction of the whole muscle. Studies are also required to determine whether it is sufficient to biopsy only one muscle (and if so, which is optimal), or whether there are differential effects of aging in various muscle groups that would preclude extrapolating from one muscle to all muscles in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle torque in young and older untrained and endurance-trained men.

Plantar flexor torque was measured in 24 young (25 +/- 1.4 y) and older (62 +/- 2 y) untrained and endurance-trained men to test the hypothesis that age-associated declines in muscle function would be attenuated in older men who also endurance trained. Endurance-trained subjects averaged 7-9 h/wk of aerobic activity for 10-12 years. These subjects had not engaged in resistance training previously in the past 10 years. Plantar flexor torque was measured at velocities between 0 and 5.23 rads. s-1. In absolute terms, maximal isometric torque was 23% lower in older men compared to young men, regardless of their training status. On the other hand, relative measures of isometric strength (i.e., torque.muscle cross-sectional area-1 and torque.muscle volume-1) were similar in young and older men but were higher in trained than in untrained men. Isokinetic torque.muscle cross-sectional area-1 and torque.muscle volume-1 was greater at contraction velocities of 0.26-2.09 rads.s-1 for trained subjects. These data suggest that endurance training does not attenuate the age-associated loss of muscle mass or absolute strength. However, endurance training might reduce the extent of loss of relative strength because torque-muscle cross-sectional area-1 and torque.muscle volume-1 are greater in endurance-trained older men than in untrained older men.

Effect of theophylline on substrate metabolism during exercise.

We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.

Fat metabolism during high-intensity exercise in endurance-trained and untrained men.

To determine whether trained individuals rely more on fat than untrained persons during high-intensity exercise, six endurance-trained men and six untrained men were studied during 30 minutes of exercise at 75% to 80% maximal oxygen consumption (VO2max). The rates of appearance (Ra) and disappearance (Rd) of glycerol and free fatty acids (FFAs) were determined using [1,1,2,3,3-2H]glycerol and [1-13C]palmitate, respectively, whereas the overall rate of fatty acid oxidation was determined using indirect calorimetry. During exercise, the whole-body rate of lipolysis (ie, glycerol Ra) was higher in the trained group (7.1 +/- 1.2 v 4.5 +/- 0.7 micromol x min(-1) x kg(-1), P < .05), as was the Ra (approximately Rd) of FFA (9.0 +/- 0.9 v 5.0 +/- 1.0 micromol x min(-1) x kg(-1), P < .001). FFA utilization was higher in trained subjects even when expressed as a percentage of total energy expenditure (10% +/- 1% v 7% +/- 1%, P < .05). However, this difference in plasma FFA flux could not account for all of the difference in fatty acid oxidation between trained and untrained subjects (20.8 +/- 3.3 v 7.9 +/- 1.6 micromol x min(-1) x kg(-1), or 23% +/- 3% v 13% +/- 2% of total energy expenditure, both P < .05). Thus, the oxidation of fatty acids derived from some other source also must have been greater in the trained men. We conclude that trained athletes use more fat than untrained individuals even during intense exercise performed at the same percentage of VO2max. The additional fatty acids appear to be derived from both adipose tissue and, presumably, intramuscular triglyceride stores.

Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion.

Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously ("euglycemic clamp"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of carbohydrate feedings during high-intensity exercise.

To determine the upper limits of steady-state exercise performance and carbohydrate oxidation late in exercise, seven trained men were studied on two occasions during prolonged cycling that alternated every 15 min between approximately 60% and approximately 85% of VO2max. When fed a sweet placebo throughout exercise, plasma glucose and respiratory exchange ratio (R) declined (P less than 0.05) from 5.0 +/- 0.1 mM and 0.91 +/- 0.01 after 30 min (i.e., at 85% VO2max) to 3.7 +/- 0.3 mM and 0.79 +/- 0.01 at fatigue (i.e., when the subjects were unable to continue exercise at 60% VO2max). Carbohydrate feeding throughout exercise (1 g/kg at 10 min, then 0.6 g/kg every 30 min) increased plasma glucose to approximately 6 mM and partially prevented this decline in carbohydrate oxidation, allowing the men to perform 19% more work (2.74 +/- 0.13 vs. 2.29 +/- 0.09 MJ, P less than 0.05) before fatiguing. Even when fed carbohydrate, however, by the 3rd h of exercise, R had fallen from 0.92 to 0.87, accompanied by a reduction in exercise intensity from approximately 85% to approximately 75% VO2max (both P less than 0.05). These data indicate that carbohydrate feedings enable trained cyclists to exercise at up to 75% VO2max and to oxidize carbohydrate at up to 2 g/min during the later stages of prolonged intense exercise.

Assessment of methods for improving tracer estimation of non-steady-state rate of appearance.

The most common approach for estimating substrate rate of appearance (R(a)) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. (Am. J. Physiol. 187: 15-24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215-224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng. kg(-1). min(-1)) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of R(a) obtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating R(a) for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR(1)/TTR(2) approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose R(a) can be obtained with the constant-infusion technique if V = 145 ml/kg.

Glucose kinetics and substrate oxidation during exercise in the follicular and luteal phases.

The purpose of this investigation was to determine whether plasma glucose kinetics and substrate oxidation during exercise are dependent on the phase of the menstrual cycle. Once during the follicular (F) and luteal (L) phases, moderately trained subjects [peak O(2) uptake (V(O(2))) = 48.2 +/- 1.1 ml. min(-1). kg(-1); n = 6] cycled for 25 min at approximately 70% of the V(O(2)) at their respective lactate threshold (70%LT), followed immediately by 25 min at 90%LT. Rates of plasma glucose appearance (R(a)) and disappearance (R(d)) were determined with a primed constant infusion of [6,6-(2)H]glucose, and total carbohydrate (CHO) and fat oxidation were determined with indirect calorimetry. At rest and during exercise at 70%LT, there were no differences in glucose R(a) or R(d) between phases. CHO and fat oxidation were not different between phases at 70%LT. At 90%LT, glucose R(a) (28.8 +/- 4.8 vs. 33.7 +/- 4.5 micromol. min(-1). kg(-1); P < 0.05) and R(d) (28.4 +/- 4.8 vs. 34.0 +/- 4.1 micromol. min(-1). kg(-1); P < 0.05) were lower during the L phase. In addition, at 90%LT, CHO oxidation was lower during the L compared with the F phase (82.0 +/- 12.3 vs. 93.8 +/- 9.7 micromol. min(-1) .kg(-1); P < 0.05). Conversely, total fat oxidation was greater during the L phase at 90%LT (7.46 +/- 1.01 vs. 6.05 +/- 0.89 micromol. min(-1). kg(-1); P < 0.05). Plasma lactate concentration was also lower during the L phase at 90%LT concentrations (2.48 +/- 0.41 vs. 3.08 +/- 0.39 mmol/l; P < 0.05). The lower CHO utilization during the L phase was associated with an elevated resting estradiol (P < 0.05). These results indicate that plasma glucose kinetics and CHO oxidation during moderate-intensity exercise are lower during the L compared with the F phase in women. These differences may have been due to differences in circulating estradiol.

Effects of detraining on cardiovascular responses to exercise: role of blood volume.

In this study we determined whether the decline in exercise stroke volume (SV) observed when endurance-trained men stop training for a few weeks is associated with a reduced blood volume. Additionally, we determined the extent to which cardiovascular function could be restored in detrained individuals by expanding blood volume to a similar level as when trained. Maximal O2 uptake (VO2max) was determined, and cardiac output (CO2 rebreathing) was measured during upright cycling at 50-60% VO2max in eight endurance-trained men before and after 2-4 wk of inactivity. Detraining produced a 9% decline in blood volume (5,177 to 4,692 ml; P less than 0.01) during upright exercise, due primarily to a 12% lowering (P less than 0.01) of plasma volume (PV; Evans blue dye technique). SV was reduced by 12% (P less than 0.05) and VO2max declined 6% (P less than 0.01), whereas heart rate (HR) and total peripheral resistance (TPR) during submaximal exercise were increased 11% (P less than 0.01) and 8% (P less than 0.05), respectively. When blood volume was expanded to a similar absolute level in the trained and detrained state (approximately 5,500 +/- 200 ml) by infusing a 6% dextran solution in saline, the effects of detraining on cardiovascular response were reversed. SV and VO2max were increased (P less than 0.05) by PV expansion in the detrained state to within 2-4% of trained values. Additionally, HR and TPR during submaximal exercise were lowered to near trained values. These findings indicate that the decline in cardiovascular function following a few weeks of detraining is largely due to a reduction in blood volume, which appears to limit ventricular filling during upright exercise.

Exercise stroke volume relative to plasma-volume expansion.

The effects of plasma-volume (PV) expansion on stroke volume (SV) (CO2 rebreathing) during submaximal exercise were determined. Intravenous infusion of 403 +/- 21 ml of a 6% dextran solution before exercise in the upright position increased SV 11% (i.e., 130 +/- 6 to 144 +/- 5 ml; P less than 0.05) in untrained males (n = 7). Further PV expansion (i.e., 706 +/- 43 ml) did not result in a further increase in SV (i.e., 145 +/- 4 ml). SV was somewhat higher during supine compared with upright exercise when blood volume (BV) was normal (i.e., 138 +/- 8 vs. 130 +/- 6 ml; P = 0.08). PV expansion also increased SV during exercise in the supine position (i.e., 138 +/- 8 to 150 +/- 8 ml; P less than 0.05). In contrast to these observations in untrained men, PV expansion of endurance-trained men (n = 10), who were naturally PV expanded, did not increase SV during exercise in the upright or supine positions. When BV in the untrained men was increased to match that of the endurance-trained subjects, SV was observed to be 15% higher (165 +/- 7 vs. 144 +/- 5 ml; P less than 0.05), whereas mean blood pressure and total peripheral resistance were significantly lower (P less than 0.05) in the trained compared with untrained subjects during upright exercise at a similar heart rate. The present findings indicate that exercise SV in untrained men is preload dependent and that increases in exercise SV occur in response to the first 400 ml of PV expansion. It appears that approximately one-half of the difference in SV normally observed between untrained and highly endurance-trained men during upright exercise is due to a suboptimal BV in the untrained men.

Isotopic estimation of CO2 production during exercise before and after endurance training.

Endurance training reduces the rate of CO2 release (i.e., VCO2) during submaximal exercise, which has been interpreted to indicate a reduction in carbohydrate oxidation. However, decreased ventilation, decreased buffering of lactate, and/or increased fixation of CO2 could also account for a lower VCO2 after training. We therefore used a primed continuous infusion of NaH13CO3 to determine the whole body rate of appearance of CO2 (RaCO2) in seven men during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2peak) before and after endurance training. RaCO2 is independent of the above-described factors affecting VCO2 but may overestimate net CO2 production due to pyruvate carboxylation and subsequent isotopic exchange in the tricarboxylic acid cycle. Training consisted of cycling at 75-100% VO2peak for 45-90 min/day, 6 days/wk, for 12 wk and increased VO2peak by 28% (P < 0.001). VCO2 during submaximal exercise was reduced from 86.8 +/- 3.7 to 76.2 +/- 4.2 mmol/min, whereas RaCO2 fell from 88.9 +/- 4.0 to 76.4 +/- 4.4 mmol/min (both P < 0.001). VCO2 and RaCO2 were highly correlated in the untrained (r = 0.98, P < 0.001) and trained (r = 0.99, P < 0.001) states, as were individual changes in VCO2 and RaCO2 with training (r = 0.88, P < 0.01). These results support the hypothesis that endurance training decreases CO2 production during exercise. The magnitude and direction of this change cannot be explained by reported training-induced alterations in amino acid oxidation, indicating that it must be the result of a decrease in carbohydrate oxidation and an increase in fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise metabolism at different time intervals after a meal.

To determine how long a meal will affect the metabolic response to exercise, nine endurance-trained and nine untrained subjects cycled for 30 min at 70% of peak O2 consumption (VO2 peak) 2, 4, 6, 8, and 12 h after eating 2 g carbohydrate/kg body wt. In addition, each subject completed 30 min of cycling 4 h after the meal at an intensity that elicited a respiratory exchange ratio (RER) of 0.94-0.95. During exercise after 2 and 4 h of fasting, carbohydrate oxidation was elevated 13-15% compared with the response to exercise after an 8- and 12-h fast (P less than 0.01). The increase in blood glycerol concentration during exercise (30 to 0 min) was linearly related to the length of fasting (r = 0.99; P less than 0.01). In all subjects, plasma glucose concentration declined 17-21% during exercise after 2 h of fasting (P less than 0.01). Plasma glucose concentration also declined (15-25%) during exercise in the trained subjects after 4 and 6 h of fasting (P less than 0.05) but did not change in the untrained subjects. However, the decline in plasma glucose concentration was similar (14%) in the two groups when the exercise intensity was increased in the trained subjects (i.e., 78 +/- 1% VO2 peak) and decreased in the untrained subjects (i.e., 65 +/- 3% VO2 peak) to elicit a similar RER.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans.

In humans, endurance training reduces the rates of glucose production and utilization during moderate-intensity exercise. It is uncertain, however, whether this is also true during high-intensity exercise. Accordingly, we studied eight endurance-trained cyclists and eight untrained subjects during 30 min of cycling at approximately 80% of maximal oxygen uptake (VO2max). Rates of glucose appearance (Ra) and disappearance (Rd) were determined using a primed, continuous infusion of [6,6-2H]glucose. Average glucose Ra during exercise did not differ in the trained and untrained subjects (34.3 +/- 3.6 vs. 36.0 +/- 1.7 mumol.min-1.kg-1; mean +/- SE; P, not significant). Plasma insulin, glucagon, norepinephrine, and epinephrine concentrations were also similar in the two groups. In contrast, glucose Rd during exercise was 19% lower in the trained compared with the untrained subjects (27.0 +/- 2.6 vs. 33.2 +/- 1.5 mumol.min-1.kg-1; P < 0.001). Consequently, during exercise, plasma glucose concentration rose significantly (P < 0.05) in the trained subjects but did not change in the untrained subjects. We conclude that utilization of plasma glucose is lower in trained subjects during high-intensity exercise, even when the exercise is performed at the same relative (and therefore a higher absolute) intensity as in the untrained state. Hyperglycemia in trained subjects during intense exercise appears to be due to this lower rate of glucose utilization rather than a higher rate of glucose production.

Substrate usage during prolonged exercise following a preexercise meal.

The effect of a high-carbohydrate meal 4 h before 105 min of exercise at 70% of maximal O2 uptake was determined in seven endurance-trained cyclists and compared with exercise following a 16-h fast. The preexercise meal produced a transient elevation of plasma insulin and blood glucose, which returned to fasting basal levels prior to the initiation of exercise. The meal also resulted in a 42% elevation (P less than 0.05) of glycogen within the vastus lateralis at the beginning of exercise. The 1st h of exercise when subjects were fed was characterized by a 13-25% decline (P less than 0.05) in blood glucose concentration, a suppression of the normal increase in plasma free fatty acids and blood glycerol, and a 45% (P less than 0.05) greater rate of carbohydrate oxidation compared with exercise when subjects were fasted. After 105 min of exercise, there were no significant differences when subjects were fed or fasted regarding blood glucose levels, rate of carbohydrate oxidation, or muscle glycogen concentration. The greater muscle glycogen utilization (97 +/- 18 vs. 64 +/- 8 mmol glucosyl units X kg-1; P less than 0.05) and carbohydrate oxidation when subjects were fed appeared to be derived from the glycogen synthesized following the meal. These results indicate that preexercise feedings alter substrate availability despite a return of plasma insulin to fasting levels prior to exercise and that these effects persist until the 2nd h of exercise.

Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men.

To assess the effects of endurance training on plasma glucose kinetics during moderate-intensity exercise in men, seven men were studied before and after 12 wk of strenuous exercise training (3 days/wk running, 3 days/wk cycling). After priming of the glucose and bicarbonate pools, [U-13C] glucose was infused continuously during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2) to determine glucose turnover and oxidation. Training increased cycle ergometer peak VO2 by 23% and decreased the respiratory exchange ratio during the final 30 min of exercise from 0.89 +/- 0.01 to 0.85 +/- 0.01 (SE) (P less than 0.001). Plasma glucose turnover during exercise decreased from 44.6 +/- 3.5 mumol.kg fat-free mass (FFM)-1.min-1 before training to 31.5 +/- 4.3 after training (P less than 0.001), whereas plasma glucose clearance (i.e., rate of disappearance/plasma glucose concentration) fell from 9.5 +/- 0.6 to 6.4 +/- 0.8 ml.kg FFM-1.min-1 (P less than 0.001). Oxidation of plasma-derived glucose, which accounted for approximately 90% of plasma glucose disappearance in both the untrained and trained states, decreased from 41.1 +/- 3.4 mumol.kg FFM-1.min-1 before training to 27.7 +/- 4.8 after training (P less than 0.001). This decrease could account for roughly one-half of the total reduction in the amount of carbohydrate utilized during the final 30 min of exercise in the trained compared with the untrained state.

Determinants of endurance in well-trained cyclists.

Fourteen competitive cyclists who possessed a similar maximum O2 consumption (VO2 max; range, 4.6-5.0 l/min) were compared regarding blood lactate responses, glycogen usage, and endurance during submaximal exercise. Seven subjects reached their blood lactate threshold (LT) during exercise of a relatively low intensity (group L) (i.e., 65.8 +/- 1.7% VO2 max), whereas exercise of a relatively high intensity was required to elicit LT in the other seven men (group H) (i.e., 81.5 +/- 1.8% VO2 max; P less than 0.001). Time to fatigue during exercise at 88% of VO2 max was more than twofold longer in group H compared with group L (60.8 +/- 3.1 vs. 29.1 +/- 5.0 min; P less than 0.001). Over 92% of the variance in performance was related to the % VO2 max at LT and muscle capillary density. The vastus lateralis muscle of group L was stressed more than that of group H during submaximal cycling (i.e., 79% VO2 max), as reflected by more than a twofold greater (P less than 0.001) rate of glycogen utilization and blood lactate concentration. The quality of the vastus lateralis in groups H and L was similar regarding mitochondrial enzyme activity, whereas group H possessed a greater percentage of type I muscle fibers (66.7 +/- 5.2 vs. 46.9 +/- 3.8; P less than 0.01). The differing metabolic responses to submaximal exercise observed between the two groups appeared to be specific to the leg extension phase of cycling, since the blood lactate responses of the two groups were comparable during uphill running. These data indicate that endurance can vary greatly among individuals with an equal VO2 max.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training improves left ventricular contractile response to beta-adrenergic agonist.

To determine whether endurance exercise training can improve left ventricular function in response to beta-adrenergic stimulation, young healthy sedentary subjects (10 women and 6 men) were studied before and after 12 wk of endurance exercise training. Training consisted of 3 days/wk of interval training (running and cycling) and 3 days/wk of continuous running for 40 min. The training resulted in an increase in maximal O2 uptake from 41.0 +/- 2 to 49.3 +/- 2 ml.kg-1.min-1 (P less than 0.01). Left ventricular function was evaluated by two-dimensional echocardiography under basal conditions and during beta-adrenergic stimulation induced by isoproterenol infusion. Fractional shortening (FS) under basal conditions was unchanged after training (36 +/- 1 vs. 36 +/- 2%). During the highest dose of isoproterenol, FS was 52 +/- 1% before and 56 +/- 1% after training (P less than 0.05). At comparable changes in end-systolic wall stress (sigma es), the increase in FS induced by isoproterenol was significantly larger after training (13 +/- 1 vs. 17 +/- 2%, P less than 0.01). Furthermore there was a greater decrease in end-systolic dimension at similar changes in sigma es in the trained state during isoproterenol infusion (-4.6 +/- 0.1 mm before vs. -7.0 +/- 0.1 mm after training, P less than 0.01). There were no concurrent changes in end-diastolic dimension between the trained and untrained states during isoproterenol infusion, suggesting no significant changes in preload at comparable levels of sigma es.(ABSTRACT TRUNCATED AT 250 WORDS)