Partial restoration of dietary fat induced metabolic adaptations to training by 7 days of carbohydrate diet.

We tested the hypothesis that a shift to carbohydrate diet after prolonged adaptation to fat diet would lead to decreased glucose uptake and impaired muscle glycogen breakdown during exercise compared with ingestion of a carbohydrate diet all along. We studied 13 untrained men; 7 consumed a high-fat (Fat-CHO; 62% fat, 21% carbohydrate) and 6 a high-carbohydrate diet (CHO; 20% fat, 65% carbohydrate) for 7 wk, and thereafter both groups consumed the carbohydrate diet for an eighth week. Training was performed throughout. After 8 wk, during 60 min of exercise (71 +/- 1% pretraining maximal oxygen uptake) average leg glucose uptake (1.00 +/- 0.07 vs. 1.55 +/- 0.21 mmol/min) was lower (P < 0.05) in Fat-CHO than in CHO. The rate of muscle glycogen breakdown was similar (4.4 +/- 0.5 vs. 4.2 +/- 0.7 mmol. min(-1). kg dry wt(-1)) despite a significantly higher preexercise glycogen concentration (872 +/- 59 vs. 688 +/- 43 mmol/kg dry wt) in Fat-CHO than in CHO. In conclusion, shift to carbohydrate diet after prolonged adaptation to fat diet and training causes increased resting muscle glycogen levels but impaired leg glucose uptake and similar muscle glycogen breakdown, despite higher resting levels, compared with when the carbohydrate diet is consumed throughout training.     

Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training

To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling. Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(-1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status ( approximately 20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest ( approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75), ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 +/- 173 micromol/min) compared with pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187 +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases.     

Influence of active muscle mass on glucose homeostasis during exercise in humans

To study the effect of increasing amounts of exercising muscle mass on the relationship between glucose mobilization and peripheral glucose uptake, seven young men (23-28 yr) bicycled for 70 min at a work load of 55-60% VO2max. From minute 30 to 50, arm cranking was added and total work load increased to 82 +/- 4% VO2max. During leg exercise, hepatic glucose production (Ra) increased in parallel with peripheral glucose uptake (Rd) and euglycemia was maintained. During arm + leg exercise, Ra increased more than Rd and accordingly plasma glucose increased from 5.11 +/- 0.22 to 8.00 +/- 0.66 mmol/l (P less than 0.05). Plasma catecholamines increased three- to four-fold more during arm + leg exercise than during leg exercise. Leg glucose uptake increased with time regardless of arm cranking. Net leg lactate release during leg exercise was reverted to a net leg lactate uptake during arm + leg exercise. The rate of glycogen breakdown in exercising leg muscle was not altered by addition of arm cranking. In conclusion, when large amounts of muscle mass are active, plasma catecholamines increase sharply and mobilization of glucose exceeds peripheral glucose uptake. This indicates that mechanisms other than feedback regulation to maintain euglycemia are involved in hormonal and substrate mobilization during intense exercise in humans.     

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.     

Effects of beta-adrenergic receptor stimulation and blockade on substrate metabolism during submaximal exercise

We used beta-adrenergic receptor stimulation and blockade as a tool to study substrate metabolism during exercise. Eight moderately trained subjects cycled for 60 min at 45% of VO(2 peak) 1) during a control trial (CON); 2) while epinephrine was intravenously infused at 0.015 microg. kg(-1) x min(-1) (beta-STIM); 3) after ingesting 80 mg of propranolol (beta-BLOCK); and 4) combining beta-BLOCK with intravenous infusion of Intralipid-heparin to restore plasma fatty acid (FFA) levels (beta-BLOCK+LIPID). beta-BLOCK suppressed lipolysis (i.e., glycerol rate of appearance) and fat oxidation while elevating carbohydrate oxidation above CON (135 +/- 11 vs. 113 +/- 10 micromol x kg(-1) x min(-1); P < 0.05) primarily by increasing rate of disappearance (R(d)) of glucose (36 +/- 2 vs. 22 +/- 2 micromol x kg(-1) x min(-1); P < 0.05). Plasma FFA restoration (beta-BLOCK+LIPID) attenuated the increase in R(d) glucose by more than one-half (28 +/- 3 micromol x kg(-1) x min(-1); P < 0.05), suggesting that part of the compensatory increase in muscle glucose uptake is due to reduced energy from fatty acids. On the other hand, beta-STIM markedly increased glycogen oxidation and reduced glucose clearance and fat oxidation despite elevating plasma FFA. Therefore, reduced plasma FFA availability with beta-BLOCK increased R(d) glucose, whereas beta-STIM increased glycogen oxidation, which reduced fat oxidation and glucose clearance. In summary, compared with control exercise at 45% VO(2 peak) (CON), both beta-BLOCK and beta-STIM reduced fat and increased carbohydrate oxidation, albeit through different mechanisms.     

Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise. Pyruvate dehydrogenase

This study investigated the effect of reduced free fatty acid (FFA) availability on pyruvate dehydrogenase activation (PDHa) and carbohydrate metabolism during moderate aerobic exercise. Eight active male subjects cycled for 40 min at 55% Vo(2 peak) on two occasions. During one trial, subjects ingested 20 mg/kg body mass of the antilipolytic drug nicotinic acid (NA) during the hour before exercise to reduce FFA. Nothing was ingested in the control trial (CON). Blood and expired gas measurements were obtained throughout the trials, and muscle biopsy samples were obtained immediately before exercise and at 5, 20, and 40 min of exercise. Plasma FFA were lower in the NA trial (0.13 +/- 0.01 vs. 0.48 +/- 0.03 mM, P < 0.05), and the respiratory exchange ratio (RER) was increased with NA (0.93 +/- 0.01 vs. 0.89 +/- 0.01, P < 0.05), resulting in a 14.5 +/- 1.8% increase in carbohydrate oxidation compared with CON. PDHa increased rapidly in both trials at exercise onset but was approximately 15% higher (P < 0.05) throughout exercise in the NA trial (2.44 +/- 0.19 and 2.07 +/- 0.12 mmol x kg wet muscle(-1) x min(-1) for NA and CON at 40 min). Muscle glycogenolysis was 15.3 +/- 9.6% greater in the NA trial vs. the CON trial but did not reach statistical significance. Glucose 6-phosphate contents were elevated (P < 0.05) in the NA trial at 30 and 40 min of exercise, but pyruvate and lactate contents were unaffected. These data demonstrate that the reduction of exogenous FFA availability increased the activation of PDH and carbohydrate oxidation during moderate aerobic exercise in men. The increased activation of PDH was not explained by changes in muscle pyruvate or the ATP/ADP ratio but may be related to a decrease in the NADH/NAD(+) ratio or an epinephrine-induced increase in calcium concentration.     

No effect of mild heat stress on the regulation of carbohydrate metabolism at the onset of exercise.

To investigate the influence of heat stress on the regulation of skeletal muscle carbohydrate metabolism, six active, but not specifically trained, men performed 5 min of cycling at a power output eliciting 70% maximal O2 uptake in either 20 degrees C (Con) or 40 degrees C (Heat) after 20 min of passive exposure to either environmental condition. Although muscle temperature (T(mu)) was similar at rest when comparing trials, 20 min of passive exposure and 5 min of exercise increased (P < 0.05) T(mu) in Heat compared with Con (37.5 +/- 0.1 vs. 36.9 +/- 0.1 degrees C at 5 min for Heat and Con, respectively). Rectal temperature and plasma epinephrine were not different at rest, preexercise, or 5 min of exercise between trials. Although intramuscular glycogen phosphorylase and pyruvate dehydrogenase activity increased (P < 0.05) at the onset of exercise, there were no differences in the activities of these regulatory enzymes when comparing Heat with Con. Accordingly, glycogen use in the first 5 min of exercise was not different when comparing Heat with Con. Similarly, no differences in intramuscular concentrations of glucose 6-phosphate, lactate, pyruvate, acetyl-CoA, creatine, phosphocreatine, or ATP were observed at any time point when comparing Heat with Con. These results demonstrate that, whereas mild heat stress results in a small difference in contracting T(mu), it does not alter the activities of the key regulatory enzymes for carbohydrate metabolism or glycogen use at the onset of exercise, when plasma epinephrine levels are unaltered.     

Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog

The aim of this study was to examine the role of nitric oxide (NO) in the control of cardiac metabolism at 60 days of pregnancy (P60) in the dog. There was a basal increase in diastolic coronary blood flow during pregnancy and a statistically significant increase in cardiac output (55 +/- 4%) and in cardiac NOx production (44 +/- 4 to 59 +/- 3 nmol/min, P < 0.05). Immunohistochemistry of the left ventricle showed an increase in endothelial nitric oxide synthase staining in the endothelial cells at P60. NO-dependent coronary vasodilation (Bezold-Jarisch reflex) was increased by 20% and blocked by N(G)-nitro-l-arginine methyl ester (l-NAME). Isotopically labeled substrates were infused to measure oleate, glucose uptake, and oxidation. Glucose oxidation was not significantly different in P60 hearts (5.4 +/- 0.5 vs. 6.2 +/- 0.4 micromol/min) but greatly increased in response to l-NAME injection (to 19.9 +/- 0.9 micromol/min, P < 0.05). Free fatty acid (FFA) oxidation was increased in P60 (from 5.3 +/- 0.6 to 10.4 +/- 0.5 micromol/min, P < 0.05) and decreased in response to l-NAME (to 4.5 +/- 0.5 micromol/min, P < 0.05). There was an increased oxidation of FFA for ATP production but no change in the respiratory quotient during pregnancy. Genes associated with glucose and glycogen metabolism were downregulated, whereas genes involved in FFA oxidation were elevated. The acute inhibition of NO shifts the heart away from FFA and toward glucose metabolism despite the downregulation of the carbohydrate oxidative pathway. The increase in endothelium-derived NO during pregnancy results in a tonic inhibition of glucose oxidation and reliance on FFA uptake and oxidation to support ATP synthesis in conjunction with upregulation of FFA metabolic enzymes.     

Preexercise medium-chain triglyceride ingestion does not alter muscle glycogen use during exercise.

This investigation determined whether ingestion of a tolerable amount of medium-chain triglycerides (MCT; approximately 25 g) reduces the rate of muscle glycogen use during high-intensity exercise. On two occasions, seven well-trained men cycled for 30 min at 84% maximal O(2) uptake. Exactly 1 h before exercise, they ingested either 1) carbohydrate (CHO; 0.72 g sucrose/kg) or 2) MCT+CHO [0.36 g tricaprin (C10:0)/kg plus 0.72 g sucrose/kg]. The change in glycogen concentration was measured in biopsies taken from the vastus lateralis before and after exercise. Additionally, glycogen oxidation was calculated as the difference between total carbohydrate oxidation and the rate of glucose disappearance from plasma (R(d) glucose), as measured by stable isotope dilution techniques. The change in muscle glycogen concentration was not different during MCT+CHO and CHO (42.0 +/- 4.6 vs. 38.8 +/- 4.0 micromol glucosyl units/g wet wt). Furthermore, calculated glycogen oxidation was also similar (331 +/- 18 vs. 329 +/- 15 micromol. kg(-1). min(-1)). The coingestion of MCT+CHO did increase (P < 0.05) R(d) glucose at rest compared with CHO (26.9 +/- 1.5 vs. 20.7 +/- 0. 7 micromol.kg(-1). min(-1)), yet during exercise R(d) glucose was not different during the two trials. Therefore, the addition of a small amount of MCT to a preexercise CHO meal did not reduce muscle glycogen oxidation during high-intensity exercise, but it did increase glucose uptake at rest.     

Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability.

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 approximately 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.     

Effect of carbohydrate ingestion on glycogen resynthesis in human liver and skeletal muscle, measured by (13)C MRS

This study investigated the effect of carbohydrate (CHO) ingestion on postexercise glycogen resynthesis, measured simultaneously in liver and muscle (n = 6) by (13)C magnetic resonance spectroscopy, and subsequent exercise capacity (n = 10). Subjects cycled at 70% maximal oxygen uptake for 83 +/- 8 min on six separate occasions. At the end of exercise, subjects ingested 1 g/kg body mass (BM) glucose, sucrose, or placebo (control). Resynthesis of glycogen over a 4-h period after treatment ingestion was measured on the first three occasions, and subsequent exercise capacity was measured on occasions four through six. No glycogen was resynthesized during the control trial. Liver glycogen resynthesis was evident after glucose (13 +/- 8 g) and sucrose (25 +/- 5 g) ingestion, both of which were different from control (P < 0.01). No significant differences in muscle glycogen resynthesis were found among trials. A relationship between the CHO load (g) and change in liver glycogen content (g) was evident after 30, 90, 150, and 210 min of recovery (r = 0.59-0. 79, P < 0.05). Furthermore, a modest relationship existed between change in liver glycogen content (g) and subsequent exercise capacity (r = 0.53, P < 0.05). However, no significant difference in mean exercise time was found (control: 35 +/- 5, glucose: 40 +/- 5, and sucrose: 46 +/- 6 min). Therefore, 1 g/kg BM glucose or sucrose is sufficient to initiate postexercise liver glycogen resynthesis, which contributes to subsequent exercise capacity, but not muscle glycogen resynthesis.     

Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate

The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high-carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle.     

Heat stress increases muscle glycogen use but reduces the oxidation of ingested carbohydrates during exercise.

The aim of the present study was to test the hypothesis that the oxidation rate of ingested carbohydrate (CHO) is impaired during exercise in the heat compared with a cool environment. Nine trained cyclists (maximal oxygen consumption 65 +/- 1 ml x kg body wt(-1) x min(-1)) exercised on two different occasions for 90 min at 55% maximum power ouptput at an ambient temperature of either 16.4 +/- 0.2 degrees C (cool trial) or 35.4 +/- 0.1 degrees C (heat trial). Subjects received 8% glucose solutions that were enriched with [U-13C]glucose for measurements of exogenous glucose, plasma glucose, liver-derived glucose and muscle glycogen oxidation. Exogenous glucose oxidation during the final 30 min of exercise was significantly (P < 0.05) lower in the heat compared with the cool trial (0.76 +/- 0.06 vs. 0.84 +/- 0.05 g/min). Muscle glycogen oxidation during the final 30 min of exercise was increased by 25% in the heat (2.07 +/- 0.16 vs. 1.66 +/- 0.09 g/min; P < 0.05), and liver-derived glucose oxidation was not different. There was a trend toward a higher total CHO oxidation and a lower plasma glucose oxidation in the heat although this did not reach statistical significance (P = 0.087 and P = 0.082, respectively). These results demonstrate that the oxidation rate of ingested CHO is reduced and muscle glycogen utilization is increased during exercise in the heat compared with a cool environment.     

Muscle metabolic, SR Ca(2+) -cycling responses to prolonged cycling, with and without glucose supplementation.

This study investigated the effects of prolonged exercise, with and without glucose supplementation, on metabolism and sarcoplasmic reticulum (SR) Ca(2+)-handling properties in working vastus lateralis muscle. Fifteen untrained volunteers [peak O(2) consumption (Vo(2peak)) = 3.45 +/- 0.17 l/min; mean +/- SE] cycled at approximately 60% Vo(2peak) on two occasions, during which they were provided with either an artificially sweetened placebo beverage (NG) or a 6% glucose (G) beverage (~1.00 g carbohydrate/kg body mass). Beverage supplementation started at 30 min of exercise and continued every 15 min thereafter. SR Ca(2+) handling, metabolic, and substrate responses were assessed in tissue extracted from the vastus lateralis at rest, after 30 min and 90 min of exercise, and at fatigue in both conditions. Plasma glucose during G was 15-23% higher (P < 0.05) than those observed during NG following 60 min of exercise until fatigue. Cycle time to fatigue was increased (P < 0.05) by approximately 19% during G (137 +/- 7 min) compared with NG (115 +/- 6 min). Prolonged exercise reduced (P < 0.05) maximal Ca(2+)-ATPase activity (-18.4%), SR Ca(2+) uptake (-27%), and both Phase 1 (-22.2%) and Phase 2 (-34.2%) Ca(2+)-release rates during NG. The exercise-induced reductions in SR Ca(2+)-cycling properties were not altered during G. The metabolic responses to exercise were all unaltered by glucose supplementation, since no differences in respiratory exchange ratios, carbohydrate and lipid oxidation rates, and muscle metabolite and glycogen contents were observed between NG and G. These results indicate that the maintenance of blood glucose homeostasis by glucose supplementation is without effect in modifying the muscle metabolic, endogenous glycogen, or SR Ca(2+)-handling responses.     

Glucose infusion attenuates endogenous glucose production and enhances glucose use of horses during exercise.

We examined the effects of increased glucose availability on glucose kinetics and substrate utilization in horses during exercise. Six conditioned horses ran on a treadmill for 90 min at 34 +/- 1% of maximum oxygen uptake. In one trial [glucose (Glu)], glucose was infused at a mean rate of 34.9 +/- 1.1 micromol. kg(-1). min(-1), whereas in the other trial [control (Con)] an equivalent volume of isotonic saline was infused. Plasma glucose increased during exercise in Glu (90 min: 8.3 +/- 1.7 mM) but was largely unchanged in Con (90 min: 5.1 +/- 0.4 mM). In Con, hepatic glucose production (HGP) increased during exercise, reaching a peak of 38.6 +/- 2.7 micromol. kg(-1). min(-1) after 90 min. Glucose infusion partially suppressed (P < 0.05) the rise in HGP (peak value 25.8 +/- 3.3 micromol. kg(-1). min(-1)). In Con, glucose rate of disappearance (R(d)) rose to a peak of 40.4 +/- 2.9 micromol. kg(-1). min(-1) after 90 min; in Glu, augmented glucose utilization was reflected by values for glucose R(d) that were twofold higher (P < 0.001) than in Con between 30 and 90 min. Total carbohydrate oxidation was higher (P < 0.05) in Glu (187.5 +/- 8.5 micromol. kg(-1). min(-1)) than in Con (159.2 +/- 7.3 micromol. kg(-1).min(-1)), but muscle glycogen utilization was similar between trials. We conclude that an increase in glucose availability in horses during low-intensity exercise 1) only partially suppresses HGP, 2) attenuates the decrease in carbohydrate oxidation during such exercise, but 3) does not affect muscle glycogen utilization.     

Regulation of fuel metabolism by preexercise muscle glycogen content and exercise intensity.

To date, the results of studies that have examined the effects of altering preexercise muscle glycogen content and exercise intensity on endogenous carbohydrate oxidation are equivocal. Differences in the training status of subjects between investigations may, in part, explain these inconsistent findings. Accordingly, we determined the relative effects of exercise intensity and carbohydrate availability on patterns of fuel utilization in the same subjects who performed a random order of four 60-min rides, two at 45% and two at 70% of peak O(2) uptake (Vo(2 peak)), after exercise-diet intervention to manipulate muscle glycogen content. Preexercise muscle glycogen content was 596 +/- 43 and 202 +/- 21 mmol/kg dry mass (P < 0.001) for high-glycogen (HG) and low-glycogen (LG) conditions, respectively. Respiratory exchange ratio was higher for HG than LG during exercise at both 45% (0.85 +/- 0.01 vs. 0.74 +/- 0.01; P < 0.001) and 70% (0.90 +/- 0.01 vs. 0.79 +/- 0.01; P < 0.001) of Vo(2 peak). The contribution of whole body muscle glycogen oxidation to energy expenditure differed between LG and HG for exercise at both 45% (5 +/- 2 vs. 45 +/- 5%; P < 0.001) and 70% (25 +/- 3 vs. 60 +/- 3%; P < 0.001) of Vo(2 peak). Yet, despite marked differences in preexercise muscle glycogen content and its subsequent utilization, rates of plasma glucose disappearance were similar under all conditions. We conclude that, in moderately trained individuals, muscle glycogen availability (low vs. high) does not influence rates of plasma glucose disposal during either low- or moderate-intensity exercise.     

Substrate utilization in leg muscle of men after heat acclimation

Eight men were heat acclimated (39.6 degrees C and 29.2% rh) for 8 days to examine changes in substrate utilization. A heat exercise test (HET), (cycling for 60 min; 50% maximal O2 consumption) was performed before (UN-HET) and after (ACC-HET) the acclimation period. Muscle glycogen utilization (67.0 vs. 37.6 mmol/kg wet wt), respiratory exchange ratio (0.85 +/- 0.002 vs. 0.83 +/- 0.001), and calculated rate of carbohydrate oxidation (75.15 +/- 1.38 vs. 64.80 +/- 1.52 g/h) were significantly reduced (P less than 0.05) during the ACC-HET. Significantly lower (P less than 0.05) femoral venous glucose (15, 30, and 45 min) and lactate (15 min) levels were observed during the ACC-HET. No differences were observed in plasma free fatty acid (FFA) and glycerol concentrations or glucose, lactate and glycerol arteriovenous uptake/release between tests. A small but significant increase (P less than 0.05) above resting levels in FFA uptake was observed during the ACC-HET. Leg blood flow was slightly greater (P greater than 0.05) during the ACC-HET (4.64 +/- 0.13 vs. 4.80 +/- 0.13 l/min). These findings indicate a reduced use of muscle glycogen following heat acclimation. However, the decrease is not completely explained by a shift toward greater lipid oxidation or increased blood flow.     

Effect of increased plasma free fatty acid concentrations on muscle metabolism in exercising men

The effect of increasing plasma concentrations of free fatty acids on substrate utilization in muscle during exercise was investigated in 11 healthy young males. One hour of dynamic knee extension at 80% of knee-extensor maximal work capacity was performed first with one leg and then with the other leg during infusion of Intralipid and heparin. Substrate utilization was assessed from arterial and femoral venous blood sampling as well as from muscle biopsies. Intralipid infusion increased mean plasma free fatty acid concentrations from 0.54 +/- 0.08 to 1.12 +/- 0.09 (SE) mM. Thigh glucose uptake during rest, exercise, and recovery was decreased by 64, 33, and 42%, respectively, by Intralipid, whereas muscle glycogen breakdown and release of lactate, pyruvate, and citrate were unaffected. Concentrations of glucose, glucose 6-phosphate, and lactate in muscle before and at termination of exercise were unaffected by Intralipid. During exercise, net leg uptake of plasma free fatty acids was not measurably increased by Intralipid, whereas uptake of ketone bodies was. Local respiratory quotient across the leg was not changed by Intralipid (control 0.87 +/- 0.02, Intralipid 0.86 +/- 0.02). Arterial concentrations of insulin, norepinephrine, and epinephrine were similar in the two trials. It is concluded that at rest and during exercise at a moderate intensity (requiring approximately equal contributions from fat and carbohydrate metabolism), muscle carbohydrate metabolism is affected only with regard to uptake of glucose when plasma concentrations of lipid and lipid metabolites are increased. This effect may be by direct inhibition of glucose transport rather than by the classic glucose-fatty acid cycle.     

Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal muscle during prolonged exercise.

Prolonged moderate-intensity exercise is characterized by a progressive reduction in carbohydrate oxidation and concomitant increase in fat oxidation. Pyruvate dehydrogenase (PDH) controls the entry of pyruvate into oxidative pathways and is a rate-limiting enzyme for carbohydrate metabolism. PDH is controlled by the activities of a kinase (PDK, inhibitory) and phosphatase (stimulatory). To test the hypothesis that increased PDK activity was associated with decreased PDH activity and carbohydrate oxidation during an acute exercise bout, seven recreationally active men completed 4 h of cycle exercise at 55% peak oxygen consumption. Muscle samples were obtained before and at 10 min and 4 h of exercise for the measurement of PDH activity and the extraction of intact mitochondria for the measurements of PDK activity and PDK-2 and PDK-4 protein expression. Carbohydrate oxidation was reduced (P < 0.05) with exercise duration. Muscle glycogen content was lower (P < or = 0.05) at 4 h compared with rest and there was no change in muscle pyruvate content from 10 to 240 min during exercise (10 min: 0.28 +/- 0.05; 240 min: 0.35 +/- 0.09 mmol/kg dry muscle). PDH activity increased (P < 0.05) above resting values at 10 min (2.86 +/- 0.26 mmol.min(-1).kg wet muscle(-1)), but was lower than 10 min after 4 h (2.23 +/- 0.24 mmol.min(-1).kg wet muscle(-1)) of exercise. PDK-2 and PDK-4 protein expression was not different from rest at 10 min and 4 h of exercise. PDK activity at rest averaged 0.081 +/- 0.016 min(-1), was similar at 10 min, and increased (P < 0.05) to 0.189 +/- 0.013 min(-1) at 4 h. Although reduced glycolytic flux may have played a role in decreasing carbohydrate oxidation, the results suggest that increased PDK activity contributed to the reduction in PDH activity and carbohydrate oxidation late in prolonged exercise. The increased PDK activity was independent of changes in intra-mitochondrial effectors, and PDK-2 and PDK-4 protein content, suggesting that it was caused by a change in the specific activity of the existing kinases.     

Effect of carbohydrate ingestion on metabolism during running and cycling.

The effects of carbohydrate or water ingestion on metabolism were investigated in seven male subjects during two running and two cycling trials lasting 60 min at individual lactate threshold using indirect calorimetry, U-14C-labeled tracer-derived measures of the rates of oxidation of plasma glucose, and direct determination of mixed muscle glycogen content from the vastus lateralis before and after exercise. Subjects ingested 8 ml/kg body mass of either a 6.4% carbohydrate-electrolyte solution (CHO) or water 10 min before exercise and an additional 2 ml/kg body mass of the same fluid after 20 and 40 min of exercise. Plasma glucose oxidation was greater with CHO than with water during both running (65 +/- 20 vs. 42 +/- 16 g/h; P < 0.01) and cycling (57 +/- 16 vs. 35 +/- 12 g/h; P < 0.01). Accordingly, the contribution from plasma glucose oxidation to total carbohydrate oxidation was greater during both running (33 +/- 4 vs. 23 +/- 3%; P < 0.01) and cycling (36 +/- 5 vs. 22 +/- 3%; P < 0.01) with CHO ingestion. However, muscle glycogen utilization was not reduced by the ingestion of CHO compared with water during either running (112 +/- 32 vs. 141 +/- 34 mmol/kg dry mass) or cycling (227 +/- 36 vs. 216 +/- 39 mmol/kg dry mass). We conclude that, compared with water, 1) the ingestion of carbohydrate during running and cycling enhanced the contribution of plasma glucose oxidation to total carbohydrate oxidation but 2) did not attenuate mixed muscle glycogen utilization during 1 h of continuous submaximal exercise at individual lactate threshold.