Interleukin-6 release is higher across arm than leg muscles during whole-body exercise

Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen subjects (10 men and six women, with body mass index 24 ± 1 kg m(-2) and peak oxygen uptake 3.4 ± 0.6 l min(-1)) performed a 90 min combined arm and leg cycle exercise at 60% of maximal oxygen uptake. The subjects arrived at the laboratory having fasted overnight, and catheters were placed in the femoral artery and vein and in the subclavian vein. During exercise, arterial and venous limb blood was sampled and arm and leg blood flow were measured by thermodilution. Lean limb mass was measured by dual-energy X-ray absorbtiometry scanning. Before and after exercise, biopsies were obtained from vastus lateralis and deltoideus. During exercise, IL-6 release was similar between men and women and higher (P < 0.05) from arms than legs (1.01 ± 0.42 and 0.33 ± 0.12 ng min(-1) (kg lean limb mass)(-1), respectively). Blood flow (425 ± 36 and 554 ± 35 ml min(-1) (kg lean limb mass)(-1)) and fatty acid uptake (26 ± 7 and 47 ± 7 μmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 μmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P < 0.05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding of a markedly higher IL-6 release from the exercising arm compared with the leg during whole-body exercise was not directly correlated to release or uptake of exogenous substrate, nor to muscle glycogen utilization.     

Carbohydrate utilization by exercising muscle following pre-exercise glucose ingestion

The effect on exercising muscle metabolism of prior ingestion of 200 g glucose was examined in six healthy subjects during 40 min leg exercise at 30% of maximal oxygen uptake. Leg glucose uptake during exercise was on average two- to three-fold higher after glucose (E + G) compared to exercise without glucose (E) and could account for 44-48% of the oxidative leg metabolism (control value: 19%, P less than 0.05-0.01). In contrast to E, which was associated with a significant release of leg lactate, pyruvate and alanine, E + G gave no leg production of lactate or alanine and an uptake of pyruvate. The respiratory exchange ratios (R) were higher during G + E and corresponded to a carbohydrate oxidation of 54-69% as against 46-49% (P less than 0.05-0.01) during E. Estimated from R-values and leg oxygen and glucose uptakes, carbohydrate oxidation during G less than E was almost completely accounted for by blood glucose. During E, on the other hand, carbohydrate oxidation exceeded leg glucose uptake, indicating a small but significant muscle glycogen breakdown (P less than 0.01). The rate of glycogen utilization during E or G + E was too small to be detected by direct measurements of muscle glycogen content. The results demonstrate that glucose ingestion prior to light exercise is followed by increased uptake and more efficient oxidation of glucose, as well as by insignificant muscle glycogen degradation by exercising muscle. Although the present findings suggest a glycogen-conserving effect of glucose ingestion under these conditions, the main fuel shift is from fat to glucose oxidation.     

Histamine-receptor blockade reduces blood flow but not muscle glucose uptake during postexercise recovery in humans

Skeletal muscle vasodilatation persists following a single bout of exercise and can potentially influence glucose uptake by recovering muscle. To investigate whether blood flow is a rate-limiting component in postexercise muscle glucose uptake, we tested the hypothesis that oral ingestion of H(1)- and H(2)-receptor antagonists, known to attenuate the sustained postexercise vasodilatation, would reduce leg glucose uptake after a bout of cycling. Healthy, recreationally active subjects (n = 8) exercised for 1 h at 60% of peak oxygen consumption on each of two days, with (blockade) and without (control) histamine-receptor antagonism. For 2 h of recovery following exercise, arteriovenous glucose differences were assessed from the radial artery and femoral vein, and leg blood flow was measured using Doppler ultrasonography on the common femoral artery. Femoral blood flow following exercise was 65.4 ± 16.4 ml min(-1) lower on the blockade day compared with the control day (P < 0.05). Likewise, glucose delivery was 0.177 ± 0.045 mmol min(-1) lower with blockade (P < 0.05). However, histamine-receptor antagonism produced no consistent effect on leg glucose uptake following exercise, due to high interindividual variability. In conclusion, while oral ingestion of H(1)- and H(2)-receptor antagonists alters postexercise recovery by attenuating vasodilatation, leg glucose uptake is not universally affected in recreationally active individuals.     

IL-6 Gene Expression in Human Adipose Tissue in Response to Exercise – Effect of Carbohydrate Ingestion

Interleukin-6 (IL-6) is a cytokine involved in a number of immunological processes, but it is also linked to exercise and possibly energy status. During exercise, muscle IL-6 mRNA levels and plasma IL-6 levels are increased and further augmented when intramuscular glycogen levels are low. In contrast, the increase in plasma IL-6 is blunted if carbohydrate is administered, indicating a substrate-regulated induction of IL-6 in human skeletal muscle. Recent studies have demonstrated that IL-6 is also released from adipose tissue in response to an exercise bout. Furthermore, IL-6 has been demonstrated to have a lipolytic effect, thus possibly playing a role in mobilisation of energy as free fatty acids (FFA) in response to exercise. The purpose of the present study was to investigate the gene expression pattern of IL-6 in adipose tissue in response to exercise, and to determine whether gene expression was affected by the ingestion of carbohydrate. Eight male subjects performed 3 h of bicycling with ingestion of a carbohydrate drink or placebo. Fat biopsy samples and blood samples were obtained before, during and in the recovery phase of exercise. Both plasma IL-6 and adipose IL-6 mRNA levels increased in response to exercise. IL-6 gene expression was lower (   P < 0.05  ) in the CHO trial (1.98-fold increase, confidence interval (CI) 1.16–3.83) compared with the control (6.49-fold increase, CI 3.57–13.91) at end of exercise. Furthermore, CHO ingestion blunted the increase in plasma IL-6 levels (   P < 0.05  ) at end of exercise (26.0 ± 3.7 pg ml⁻¹ in the control vs. 15.6 ± 2.4 pg ml⁻¹ in the CHO trial). In conclusion, exercise results in an increase in IL-6 gene expression in adipose tissue in response to exercise, an effect that is significantly blunted by ingestion of carbohydrate.     

Effect of diet on the utilization of blood-borne and intramuscular substrates during exercise in man

20 subjects were studied at rest and during a 25 min submaximal exercise (65% of VO₂ max) on two occasions, the first preceded by a fat rich diet and the second by a carbohydrate rich diet. Oxygen uptake, respiratory exchange ratio (R) and arterial-femoral venous differences for glucose, lactate, β-hydroxybutyrate and FFA (based on the fractional extraction of ³H-palmitate) were measured at rest and during exercise. Changes in intramuscular glycogen, triglyceride and lactate concentrations were determined in muscle biopsies taken before and immediately after exercise form m. quadriceps femoris. R was lower after the fat than after the carbohydrate diet and simultaneously the FFA extraction by the exercising leg was higher. The muscle triglycerides did not changes significantly during exercise after either diet. The glucose extraction was insignificantly greater after the fat diet. The glycogen reduction was numerically smaller after the fat diet, but the difference was uncertain and difficult to evaluate due to a large variation after the carbohydrate diet. However, muscle lactate accumulation and release by the exercising leg was smaller after the fat diet, indicating a slower rate of muscle glycogenosis. It is concluded that a fat rich diet increases the relative contribution of fat to the oxidative metabolism, that this increase, to a great extent, is covered by plasma FFA and that the concomitant decrease in carbohydrate utilization concerns muscle glycogen rather than blood glucose.     

Exercise induces hepatosplanchnic release of heat shock protein 72 in humans

Physical exercise results in the appearance of heat shock protein (HSP) 72 in the circulation that precedes any increase in gene or protein expression in contracting skeletal muscle. In rodents, exercise increases liver HSP72 expression and the hepatosplanchnic viscera are known to release many acute phase proteins. In the present study, we tested the hypothesis that the splanchnic tissue beds release HSP72 during exercise. Seven male subjects performed 120 min of semi-recumbent cycling at 62 ± 2 % of maximal oxygen uptake. Blood samples were obtained simultaneously from a brachial artery, a femoral vein and the hepatic vein prior to and at 30, 60 and 120 min of exercise. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and hepatosplanchnic blood flow (HBL) was measured using indocyanine green dye. Net leg and net hepatosplanchnic HSP72 balance were calculated as the product of LBF and femoral venous-arterial HSP72 difference and the product of HBF and hepatic venous-arterial HSP72 difference, respectively. Arterial plasma HSP72 was only detected in one subject at rest but progressively appeared in the arterial samples throughout exercise such that at 120 min it was detected in all subjects (0.88 ± 0.35 pg l⁻¹;   P < 0.05  compared with rest). The contracting muscle did not, however, contribute to this increase since there was no difference in the femoral venous-arterial HSP72 concentration at any time. Rather, the increase in arterial HSP72 was accounted for, at least in part, by release from the hepatosplanchnic viscera with values increasing (   P < 0.05  ) from undetectable levels at rest to 5.2 ± 0.2 pg min⁻¹ after 120 min. These data demonstrate that the splanchnic tissues release HSP72 during exercise and this release is responsible, in part, for the elevated systemic concentration of this protein during exercise.     

Utilization of blood-borne and intramuscular substrates during continuous and intermittent exercise in man.

1. Substrate utilization in the legs during bicycle exercise was studied in five subjects when performing intermittent intense exercise (15 sec work--15 sec rest) as well as continuous exercise during 60 min, with an almost identical average power output and oxygen uptake in both situations. 2. Muscle biopsies were obtained from vastus lateralis at rest, during, and after exercise in order to determine intramuscular lipid and carbohydrate utilization. The contribution from blood-borne substrates to total oxidative metabolism was determined by arterial-femoral venous (a-fv) differences for oxygen, FFA, glucose, and lactate and leg blood flow. 3. Intermittent and continuous exercise revealed a similar glycogen depletion and the intramuscular lactate accumulation was rather small. A similar uptake of blood-borne substrate (FFA, glucose) was found in both situations whereas a release of lactate only was observed in intermittent exercise. 4. ATP and CP levels oscillated between work and rest periods in intermittent exercise but were not resynthesized to resting levels at the end of the rest periods. The mainly aerobic energy release during each work period in intermittent exercise is partly caused by myoglobin functioning as an oxygen store; this factor was calculated to be more important than ATP and CP or lactate level oscillations. 5. The metabolic response to intermittent exercise was found to be similar to that found in continuous exercise with approximately the same average power output and oxygen uptake. This indicates that some factor in the intermediary metabolism, for instance citrate, functions as a regulator retarding glycolysis and favouring lipid utilization and an aerobic energy release in intermittent exercise.     

Metabolic and hormonal responses during repeated bouts of brief and intense exercise: effects of pre-exercise glucose ingestion

We investigated metabolic and hormonal responses during repeated bouts of brief and intense exercise (a force-velocity test; Fv test) and examined the effect of glucose ingestion on these responses and on exercise performance. The test was performed twice by seven subjects [27 (2) years] according to a double-blind randomized crossover protocol. During the experimental trial (GLU), the subjects ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before starting the exercise. During the control trial (CON), the subjects received an equal volume of sweet placebo (aspartame). Exercise performance was assessed by calculating peak anaerobic power ( W˙ _an,peak). Venous plasma lactate concentration increased significantly during the Fv test (P P? W˙ _an,peak and for up to 10?min during the recovery period (P? W˙ _an,peak in GLU compared with CON (P?P? W˙ _an,peak (P? W˙ _an,peak was not significantly different between CON and GLU. In conclusion, blood glucose and insulin concentrations decreased during repeated bouts of brief and intense exercise, while blood lactate concentration increased markedly without any significant change in glucagon and epinephrine concentrations. Glucose ingestion altered metabolic and hormonal responses during the Fv test, but the performance as measured by W˙ _an,peak was not changed.     

Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise

AIM: This study evaluated if the fatigue and apathy arising during exercise with hypoglycaemia could relate to a lowering of the cerebral metabolic rates of glucose and oxygen. METHODS AND RESULTS: Six males completed 3 h of cycling with or without glucose supplementation in random order. Cerebral blood flow, metabolism and interleukin-6 (IL-6) release were evaluated with the Kety-Schmidt technique. Blood glucose was maintained during the glucose trial, while it decreased from 5.2 +/- 0.1 to 2.9 +/- 0.3 mmol L-1 (mean +/- SE) after 180 min of exercise in the placebo trial with a concomitant increase in perceived exertion (P < 0.05). During hypoglycaemia, the cerebral glucose uptake was reduced from 0.34 +/- 0.05 to 0.28 +/- 0.04 micromol g(-1) min(-1), while the cerebral uptake of beta-hydroxybutyrate increased to 5 +/- 1 pmol g(-1) min(-1) (P < 0.05). The reduced glucose uptake was accompanied by a lowering of the cerebral metabolic rate of oxygen from 1.84 +/- 0.19 mmol g(-1) min(-)1 during exercise with glucose supplementation to 1.60 +/- 0.16 mmol g(-1) min(-1) during hypoglycaemia (P < 0.05). In addition, the cerebral IL-6 release was reduced from 0.4 +/- 0.1 to 0.0 +/- 0.1 pg g(-1) min(-1) (P < 0.05). CONCLUSIONS: Exercise-induced hypoglycaemia limits the cerebral uptake of glucose, exacerbates exercise, reduces the cerebral metabolic rate of oxygen and attenuates the release of IL-6 from the brain.     

Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use

Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 ± 4% of maximal O₂ uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg⁻¹ h⁻¹) or without (CON placebo trial; water only). Continuous infusions with [U-¹³C] palmitate and [6,6-²H₂] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (R _a) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 ± 19 and 57 ± 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA R _a and subsequent plasma FFA concentrations were lower, resulting in a 34 ± 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 ± 21 and 78 ± 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men.     

Metabolism in exercising arm vs. leg muscle

Arm and leg metabolism were compared by arterial and venous catheterization and blood flow measurements (by dye dilution techniques) in two groups of subjects performing 30-min continuous arm or leg exercise of increasing intensity corresponding to approximately 30, 50 and 80% of max oxygen uptake for arm or leg exercise. The absolute work-loads were 2.5-3 times higher during leg compared to arm exercise. Heart rates were the same in both types of exercise. r-Values were 0.97-1.07 during arm exercise. Arterial noradrenaline and adrenaline levels became higher during leg compared to arm exercise (P less than 0.05-0.01). Arterial lactate concentration was 50% higher for arm exercise at the two lower intensities (P less than 0.001) and the same at the highest intensity compared to leg exercise. Arm lactate release was three times higher (P less than 0.01) or the same as leg lactate output at corresponding exercise intensities. Arm and leg glucose uptake during exercise were of the same magnitude at the lower intensities. In contrast to the leg substrate exchange, arm lactate output was higher than the simultaneous glucose uptake (P less than 0.05-0.001), indicating a relatively higher rate of glycogen degradation. In conclusion, exercising arm compared to leg muscles working at the same relative intensities utilize more carbohydrate, mainly muscle glycogen resulting in higher lactate release by the exercising extremity. This cannot solely be explained on the basis of differences in the degree of training and occurs with lower catecholamine levels compared to leg exercise.     

Glucose ingestion during endurance training in men attenuates expression of myokine receptor

Glucose ingestion during exercise attenuates the release of the myokine interleukin-6 (IL-6) from working skeletal muscle, which results in a diminished increase in plasma IL-6. Interleukin-6 receptor α (IL-6Rα) expression in skeletal muscle is induced by acute exercise, mediated in part by an increased IL-6 concentration in the bloodstream. We hypothesized that endurance training would increase the density of IL-6Rα in skeletal muscle and that glucose ingestion would attenuate the effect. Nine subjects performed 10 weeks of one-legged knee-extensor training. They trained one leg (Glc-leg) while ingesting a glucose solution (Glc) and ingested a placebo (Plc) while training the other leg (Plc-leg). Endurance training increased peak power by ∼14% and reduced the exercise-induced gene expression of IL-6 and IL-6Rα in skeletal muscle and IL-6 plasma concentration. The IL-6Rα density increased to a lesser extent in the Glc-leg, suggesting that glucose ingestion attenuates the effect of training on IL-6Rα by blunting the IL-6 response. We conclude that glucose ingestion during endurance training attenuates the increase in IL-6Rα density.     

Effect of creatine supplementation on intramuscular TCr,metabolism and performance during intermittent,supramaximal exercise in humans

This study examined the effect of (a) creatine supplementation on exercise metabolism and performance and (b) changes in intramuscular total creatine stores following a 5 day supplementation period and a 28 day wash-out period. Six men performed four exercise trials, each consisting of four 1 min cycling bouts, punctuated by 1 min of rest followed by a fifth bout to fatigue, all at a workload estimated to require 115 or 125% VO_{2, max} After three familiarization trials, one trial was conducted following a creatine monohydrate supplementation protocol (CREAT); the other after 28 d without creatine supplementation, in which the last 5 d involved placebo ingestion (CON). Intramuscular TCr was elevated (P < 0.05) in CREAT compared with the final familiarization trial (FAM3) and CON. Concentrations of this metabolite in these latter trials were not different. In addition, a main effect (P < 0.05) for treatment was observed for PCr when the data from CREAT were compared with CON. In contrast, no differences were observed in the total adenine nucleotide pool (ATP + ADP +AMP), inosine 5′-monophosphate, ammonia, lactate or glycogen when comparing CREAT with CON. Despite the differences in TCr and PCr concentrations when comparing CREAT with other trials, no difference was observed in exercise duration in the fifth work bout. These data demonstrate that creatine supplementation results in an increase in TCr but this has no effect on performance during exercise of this nature, where the creatine kinase system is not the principal energy supplier. In addition 28 d without supplementation is a sufficient time to return intramuscular TCr stores to basal levels.     

Muscle glycogen and glucose uptake during exercise in humans.

Six men were studied during 40 min of cycling exercise to examine the relationship between leg glucose uptake and muscle glycogen concentration. Exercise resulted in significant increases in leg glucose uptake, while muscle glycogen and arterial blood glucose concentrations declined. Arterial plasma insulin levels did not change significantly. There was a significant inverse relationship between muscle glycogen concentration and glucose uptake during exercise which suggests a possible regulatory influence of muscle glycogen on glucose uptake in the early stages of exercise in humans.     

Carbohydrate ingestion prior to exercise augments the exercise-induced activation of the pyruvate dehydrogenase complex in human skeletal muscle

This study examined the effect of pre-exercise carbohydrate (CHO) ingestion on pyruvate dehydrogenase complex (PDC) activation, acetyl group availability and substrate level phosphorylation (glycogenolysis and phosphocreatine (PCr) hydrolysis) in human skeletal muscle during the transition from rest to steady-state exercise. Seven male subjects performed two 10 min treadmill runs at 70 % maximum oxygen uptake (VO2,max), 1 week apart. Each subject ingested 8 ml (kg body mass (BM))-1 of either a placebo solution (CON trial) or a 5.5 % CHO solution (CHO trial) 10 min before each run. Muscle biopsy samples were obtained from the vastus lateralis at rest and immediately after each trial. Muscle PDC activity was higher at the end of exercise in the CHO trial compared with the CON trial (1.78+/-0.18 and 1.27+/-0.16 mmol min(-1) (kg wet matter (WM))(-1), respectively; P 0.05) and this was accompanied by lower acetylcarnitine (7.1+/-1.2 and 9.1+/-1.1 mmol kg(-1) (dry matter (DM))(-1) in CHO and CON, respectively; P<0.05) and citrate concentrations (0.73+/-0.05 and 0.91+/-0.10 mmol (kg DM)(-1) in CHO and CON, respectively; P<0.05). No difference was observed between trials in the rates of muscle glycogen and PCr breakdown and lactate accumulation. This is the first study to demonstrate that CHO ingestion prior to exercise augments the exercise-induced activation of muscle PDC and reduces acetylcarnitine accumulation during the transition from rest to steady-state exercise. However, those changes did not affect the contribution of substrate level phosphorylation to ATP resynthesis.     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

Summary The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177±144 ΜEq/l, m±SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization. Chercheur Qualifié of the Fonds National Belge de la Recherche Scientifique     

Effects of pre-exercise ingestion of trehalose,galactose and glucose on subsequent metabolism and cycling performance

The glycaemic and insulinaemic responses to different carbohydrates vary and these have been suggested to affect performance. The purpose of the present study was to determine the effects of pre-exercise ingestion of glucose (GLU), galactose (GAL) and trehalose (TRE) on metabolic responses at rest and during exercise and on subsequent time-trial (TT) performance. Eight well-trained male cyclists completed three exercise trials separated by at least 3 days. At 45 min before the start of exercise subjects consumed 500 ml of a beverage containing 75 g of either glucose, galactose or trehalose. The exercise trials consisted of 20 min of submaximal steady-state exercise (SS) at 65% of maximal power output immediately followed by a [mean (SEM)] 702 (25) kJ TT. Plasma glucose concentration 15 min postprandial was significantly higher in GLU compared to GAL and TRE (P<0.05). This was accompanied by a more than twofold greater rise in plasma insulin concentration in GLU compared to GAL and TRE (118% and 145%, respectively). During SS exercise four subjects in GLU and one subject in TRE developed a rebound hypoglycaemia (plasma glucose concentration less than 3.5 mmol·l^–1). No differences were observed in TT performance between the three trials. Pre-exercise ingestion of trehalose and galactose resulted in lower plasma glucose and insulin responses prior to exercise and reduced the prevalence of rebound hypoglycaemia. Despite the attenuated insulin and glucose responses at rest and during exercise following pre-exercise ingestion of galactose and trehalose, there was no difference in TT performance compared with pre-exercise ingestion of glucose. Electronic Publication     

Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle

To test the hypothesis that a decrease in intramuscular glycogen availability may stimulate heat shock protein expression, seven men depleted one leg of muscle glycogen the day before performing 4–5 h of exhaustive, two-legged knee extensor exercise at 40 % of leg peak power output. Subjects then rested for a further 3 h. Muscle biopsies were obtained from the depleted and control leg before, immediately after and 3 h into recovery from exercise. These samples were analysed for muscle glycogen, and HSP72 gene and protein expression. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery for the measurement of arterial-venous differences in serum HSP72. Plasma creatine kinase (CK) was also measured from arterial blood samples. Pre-exercise muscle glycogen content was 40 % lower in the depleted compared with the control leg and this difference was maintained throughout the experiment ( P < 0.05; main treatment effect). Neither HSP72 gene nor protein expression was different pre-exercise. However, both HSP72 gene and protein increased ( P < 0.05) post-exercise in the depleted leg, but not in the control leg. Exercise did not increase plasma CK concentrations and we were unable to detect HSP72 in the serum of any samples. These results demonstrate that while acute, concentric exercise is capable of increasing HSP72 in human skeletal muscle, it does so only when glycogen is reduced to relatively low levels. Hence, our data suggest that HSP72 protein expression is related to glycogen availability. In addition, because CK did not increase and we found no evidence of HSP72 in the venous effluent, our data suggest that skeletal muscle is impermeable to HSP72.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68 +/- 3% of their VO2 max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136 +/- 13 min v. 1st test: 110 +/- 12 min, P less than 0.01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137 +/- 13 min) than with either fructose (114 +/- 12 min) or water (116 +/- 13 min) (both P less than 0.01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467 +/- 29 mmol kg d.w.-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P less than 0.05) with the ingestion of glucose (1.3 +/- 0.4 mmol kg d.w.-1 min-1) as compared to fructose (2.1 +/- 0.5 mmol kg d.w.-1 min-1) or water (2.3 +/- 0.5 mmol kg d.w.-1 min-1). Intermittent glucose ingestion (3 X 17.5 g h-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Source and kinetics of interleukin-6 in humans during exercise demonstrated by a minimally invasive model

The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from an exercised limb impacts on metabolites in the systemic circulation. On two experimental days, at least 3 weeks apart, six healthy moderately trained male subjects performed one-legged knee-extensor exercise for 2 h at 60% of their maximal workload. On one occasion venous outflow from the exercised leg was inhibited for 18 min by inflating a cuff around the thigh as proximally as possible immediately following exercise. On the control occasion venous outflow was not inhibited. Venous blood samples were collected from an arm vein at 2-min intervals after exercise. During inhibition of venous outflow from the exercised leg systemic plasma levels of IL-6 decreased within minutes to near pre-exercise levels, whereas plasma glucose levels increased to higher levels than without the cuff. After release of the cuff, systemic levels of IL-6 increased rapidly to match levels on the control occasion. On release of the cuff, plasma levels of free fatty acids (FFAs) declined more than without the cuff. In conclusion, the observed increase in systemic IL-6 plasma concentrations during exercise can be attributed to release from the working limb. Other potential sources of IL-6 outside the working limb do not contribute significantly to the increase in plasma IL-6 levels during exercise.