Metabolism in exercising arm vs. leg muscle

Summary. 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< 0·05401). Arterial lactate concentration was 50% higher for arm exercise at the two lower intensities (P< 0·001) and the same at the highest intensity compared to leg exercise. Arm lactate release was three times higher (P< 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< 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.     

ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion

Summary. To study changes in muscle energy state during prolonged exercise, especially in relation to fatigue, muscle biopsies were obtained from seven healthy males working until exhaustion on a cycle ergometer at 68% (63–74%) of their maximal oxygen uptake. Biopsies were taken at rest, after 15 and 45 min of exercise and at exhaustion, and analysed for ATP, ADP, AMP, inosine monophosphate (IMP) and hypoxanthine content by high performance liquid chromatography (HPLC), and for creatine phosphate (CP), lactate and glycogen by enzymatic fluorometric techniques. Glycogen content at exhaustion was approximately 30% of the pre-exercise level. The CP content decreased steeply during the first 15 min of exercise (P<0·01) and continued to decrease during the rest of the exercise period (P<0·05). Pronounced increases in contents of IMP (64%P<0·001) and hypoxanthine (69%, P<0·05) were found when exhaustion was approaching. Furthermore, energy charge [EC; (ATP+0·5 ADP)/(ATP+ADP+AMP)] was decreased at exhaustion (P<0·05). The increases in IMP and hypoxanthine which occurred when exhaustion was approaching during prolonged submaximal exercise together with the decrease in EC during this phase of exercise suggest a failure of the exercising skeletal muscle to regenerate ATP at exhaustion.     

Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

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

Summary. 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<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<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<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 (3×17·5 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.     

Glucose metabolism during leg exercise in man

Arterial concentrations and net substrate exchange across the leg and splanchnic vascular bed were determined for glucose, lactate, pyruvate, and glycerol in healthy postabsorptive subjects at rest and during 40 min of exercise on a bicycle ergometer at work intensities of 400, 800, and 1200 kg-m/min.Rising arterial glucose levels and small decreases in plasma insulin concentrations were found during heavy exercise. Significant arterial-femoral venous differences for glucose were demonstrated both at rest and during exercise, their magnitude increasing with work intensity as well as duration of the exercise performed. Estimated glucose uptake by the leg increased 7-fold after 40 min of light exercise and 10- to 20-fold at moderate to heavy exercise. Blood glucose uptake could at this time account for 28-37% of total substrate oxidation by leg muscle and 75-89% of the estimated carbohydrate oxidation.Splanchnic glucose production increased progressively during exercise reaching levels 3 to 5-fold above resting values at the heavy work loads. Close agreement was observed between estimates of total glucose turnover during exercise based on leg glucose uptake and splanchnic glucose production. Hepatic gluconeogenesis-estimated from splanchnic removal of lactate, pyruvate, glycerol, and glycogenic amino acids-could supply a maximum of 25% of the resting hepatic glucose production but could account for only 6-11% of splanchnic glucose production after 40 min of moderate to heavy exercise.IT IS CONCLUDED THAT: (a) blood glucose becomes an increasingly important substrate for muscle oxidation during prolonged exercise of this type: (b) peripheral glucose utilization increases in exercise despite a reduction in circulating insulin levels: (c) increased hepatic output of glucose, primarily by means of augmented glycogenolysis, contributes to blood glucose homeostasis in exercise and provides an important source of substrate for exercising muscle.     

Acute effects of aerobic exercise intensity on arterial stiffness after glucose ingestion in young men

Arterial stiffness increases after glucose ingestion. Acute low‐ and moderate‐intensity aerobic exercise decreases arterial stiffness. However, the acute effects of 30 min of cycling at low‐ and moderate‐intensity [25% (LE trial) and 65% (ME trial) peak oxygen uptake, respectively] on arterial stiffness at 30, 60 and 120 min of a postexercise glucose ingestion. Ten healthy young men (age, 22·4 ± 0·5 years) performed LE and ME trials on separate days in a randomized controlled crossover fashion. Carotid–femoral (aortic) pulse wave velocity (PWV), femoral–ankle (leg) PWV, carotid augmentation index (AIx) and carotid blood pressure (BP) (applanation tonometry), brachial and ankle BP (oscillometric device), heart rate (HR) (electrocardiography), blood glucose (UV‐hexokinase method) and blood insulin (CLEIA method) levels were measured at before (baseline) and at 30, 60 and 120 min after the 75‐g OGTT. Leg PWV, ankle pulse pressure and BG levels significantly increased from baseline after the 75‐g OGTT in the LE trial (P<0·05), but not in the ME trial. Insulin levels and HR significantly increased from baseline after the 75‐g OGTT in both trials (P<0·05). Aortic PWV, carotid AIx, brachial BP and carotid BP did not change from baseline after the 75‐g OGTT in both trials. The present findings indicate that aerobic exercise at moderate intensity before glucose ingestion suppresses increases leg arterial stiffness after glucose ingestion.     

Availability of glycogen and plasma FFA for substrate utilization in leg muscle of man during exercise

Summary. Six men performed two-legged cycle ergometer exercise at loads demanding 2–4 and 3–4 litres O₂ min^-1 (62 and 84% of Vo₂ max) for 20 min each or to exhaustion twice with 1 h rest between. An initial glycogen difference of 28 mmol glucose units kg^-1 of thigh muscle between the two legs was produced by one-legged exercise on a previous day followed by the consumption of a low carbohydrate diet. During the 1 h rest nicotinic acid (NA) was administered to inhibit lipolysis. Total body Fo₂ was unchanged by the NA administration. Work done by each leg, indicated by force on the pedals, was equal. RQ indicated a larger oxidation of fat in the leg with low glycogen. Muscle glycogen was 15 and 10 mmol kg^-1 in the normal and low glycogen leg at the end of the first exercise bouts and 3–8 mmol kg^-1 in both legs at exhaustion. The low glycogen leg extracted lactate from the blood whereas the normal leg released lactate and the uptake of glucose from the blood was greater by the low glycogen leg. These differences between the low glycogen and control legs did not persist during the NA condition when muscle glycogen content was equal in both legs. Further, the leg glucose uptake in the control and the NA conditions was positively related to the percentage of glycogen-empty muscle fibres and inversely to the glucose-6-P0₄ concentration. Thus the magnitude of the local glycogen stores of muscle influences the uptake and use of blood-borne substrates as well as determining endurance capacity during moderate to high intensity exercise.     

No effect of carbohydrate feeding on glycogen synthase in human muscle during exercise

Summary. The effect of carbohydrate (CHO) feedings on exercise-mediated changes in glycogen synthase fractional (GSF) activity has been investigated. Subjects cycled at -70% of maximal oxygen uptake on two occasions: the first to fatigue (135±17 min; meanæ) (control, CON), and the second at the same workload and duration as the first, but with the addition of frequent ingestion of CHO during exercise (0.27 g kg^-1 body weight every 15 min). Biopsies were taken from the quadriceps femoris muscle before and immediately after exercise. Plasma glucose and insulin decreased during CON exercise, but remained elevated throughout CHO exercise (end of exercise: glucose = 4.4±0.2 mM CON vs. 5.8±0.2 CHO, P < 0.01; insulin = 9±l mU ml^-1 CON vs. 19±3 CHO, P < 0.05). Glycogen decreased to - 10% of the basal value during CON and to -20% during CHO, and there was no significant difference in net glycogenosis between treatments. GSF activity averaged 0.25±0.03 and 0.22±0.05 at rest, and increased to 0.51 ±0.08 and 0.48±0.09 after exercise in CON and CHO, respectively (P > 0.05 between treatments). It is concluded that under the present conditions CHO feedings do not alter the exercise-mediated changes in GSF activity. The increase in GSF during exercise is attributed at least in part to the decrease in muscle glycogen (which increases the suitability of GS as substrate for GS phosphatase).     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

Summary. The effect of dynamic exercise on muscle and blood ammonia (NH₃) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5·2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH₃ at rest and after submaximal exercise was (x?±SE) 0·5±0·1 mmol/kg dry muscle (d.m.) and increased to 4·1 ±0·5 mmol/kg d.m. at fatigue (P<0·001). The total adenine nucleotide (TAN) pool (TAN=ATP+ADP+AMP) did not change after submaximal exercise but decreased significantly at fatigue (P<0·01). The decrease in TAN was similar to the increase in NH₃. Muscle lactate was 3±1 mmol/kg d.m. at rest and increased to 104±5 mmol/kg d.m. at fatigue. Whole blood and plasma NH₃ did not change significantly during submaximal but both increased significantly during maximal exercise (P<0·001). During maximal exercise the leg released 7,120 μmol/min of lactate, whereas only 89 μmol/min of NH₃ were released. NH₃ accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH₃ release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P<0·001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P<0·001), respectively, during exercise. It is concluded that (1) muscle and blood NH₃ levels increase only during strenuous exercise and (2) NH₃ accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Effect of bicycle exercise on insulin absorption and subcutaneous blood flow in the normal subject

Summary. Elimination of 8 units ¹²⁵I-insulin and ^99mTc-pertechnetate from a subcutaneous depot on the thigh or the abdomen was studied at rest and during intense bicycle exercise in healthy postabsorptive volunteers. Disappearance rates of the tracers as well as plasma insulin and glucose concentrations were determined before, during and after the 20 min exercise period, and compared to corresponding values obtained during a non-exercise, control study on another day. Leg exercise caused a two-fold increase in the rate of ¹²⁵I-insulin disappearance from a leg depot (first-order rate constants rose from 0·68 ± 0·15 to 1·12 ± 0·12%·min^-1, P <0·05), but had no significant effect on the rate of disappearance from an abdominal depot (rate constants were 0·75 ±0·17 and 0·87±0·18%·min^-1 at rest and during exercise, respectively). ^99mTc-pertechnetate clearance from leg or abdomen showed no significant change during exercise, indicating that subcutaneous blood flow was unaltered. Leg, but not abdominal, injection of insulin was associated with a greater rise in plasma insulin during exercise than at rest. The average difference between exercise and control insulin area-under-curve in the leg group (1426 ± 594%·min) was significantly greater (P <0·05) than that from the abdominal group (298 ±251%· min). When the data from the two study groups were pooled, a direct relationship was found to exist between the change in ¹²⁵I-insulin disappearance rate and the change in plasma insulin concentration (r=0·61, P <0·02). Plasma glucose levels fell throughout the observation period both during the exercise and the control study, following leg as well as abdominal injection. The glucose decremental area was greater during exercise than at rest both following leg (P <0·05) and abdominal injection (P <0·01). The exercise-induced mean reduction in plasma glucose was 60% lower following abdominal injection, but this difference was not significant.     

Splanchnic and peripheral glucose and lactate metabolism during and after prolonged arm exercise.

Splanchnic and peripheral exchange of glucose and gluconeogenic substrates was examined in 12 healthy subjects during 2 h of arm or leg exercise on a bicycle ergometer and during a 40-min postexercise recovery period. The work intensity corresponded to 30% of the maximal pulmonary oxygen uptake. The regional exchange of substrates was evaluated using catheter technique and indicator dilution methods for blood flow measurements. Our findings indicate that prolonged arm exercise as compared with exercise with the legs results in a greater increase in heart rate (25-40%) and a more marked reduction in splanchnic blood flow (10-30%) as well as higher arterial concentrations of lactate, free fatty acids, and catecholamines. The respiratory exchange ratio was consistently higher with arm exercise. In addition, arm exercise results in a greater fractional extraction and utilization of glucose by exercising muscle as well as a greater hepatic gluconeogenesis from lactate and glycerol. During recovery from prolonged arm exercise, leg muscle becomes an important site of lactate release to the splanchnic bed, despite a lack of net glucose uptake by the leg. Simultaneously, arm muscle shows an increase in glucose uptake in the absence of a net release of lactate. These coincident but discordant processes in the leg and arm during recovery suggest the occurrence of a redistribution of muscle glycogen from previously resting (leg) muscle to previously exercising (arm) muscle.     

Metabolism of exercising skeletal muscle during beta1-selective adrenoceptor blockade

Summary. Concentrations of glycogen, glucose, glucose-6-phosphate and lactate in the lateral vastus muscle were measured in seven subjects before and after dynamic muscle exercise at a work load of 75% of each subject's maximal working capacity, and with and without intravenous administration of the beta₁-selective beta-adrenoceptor blocking agent, atenolol. Pulmonary oxygen uptake was measured during exercise. Heart rate and arterial blood pressure were measured throughout the study. Arterial concentrations of glucose, lactate and free fatty acids were measured at rest and during exercise. The muscle concentration of glycogen and the extent of glycogen depletion with exercise were not influenced by the beta₁-adrenoceptor blocker. Similarly, there was no change in the muscle concentrations of glucose, glucose-6-phosphate and lactate. Heart rate decreased at rest and during exercise. Arterial blood pressure was not influenced by beta-blockade. Pulmonary oxygen uptake decreased by 6·5%. The exercise induced rise in arterial blood concentration of free fatty acids was abolished by beta₁-selective beta-blockade. It is concluded that the decrease in lactate release from exercising muscles during beta₁-adrenoceptor blockade seen in other studies cannot be explained by an impaired breakdown of muscle glycogen. It may be inferred, however, that a reduced availability of free fatty acids in the exercising muscles during beta₁selective (and non-selective) beta-blockade may enhance the combustion of pyruvic acid and thereby decrease the production of lactate.     

Combined effect of coffee ingestion and repeated bouts of low-intensity exercise on fat oxidation

We investigated the effect of the combination of coffee ingestion and repeated bouts of low-intensity exercise on fat oxidation. Subjects were seven young, healthy male adults. They performed four trials: a single 30-min bout of exercise following ingestion of plain hot water (WS) or coffee (CS); a trial with three 10-min bouts of exercise separated by 10-min periods of rest following ingestion of plain hot water (WR) or coffee (CR). The coffee contained 5 mg kg⁻¹ of caffeine. All trials were performed on a cycle ergometer at 40% maximal oxygen uptake for each subject an hour after beverage ingestion. Oxygen uptake in the CS and CR trials was higher compared with the WS and WR trials at 90 min after exercise (P<0·05). Respiratory exchange ratio (RER) in the CS and CR trials was decreased during the whole recovery period compared with baseline (P<0·05), whereas no significant decreases were observed in either the WS or WR trials. Moreover, RER was significantly lower at 30 min after exercise in the CR trial than in either the WS or WR trials (P<0·05 each). Similarly, it is notable that fat oxidation rate in the CR trial was significantly higher at 30 min after exercise compared to that in the WS and WR trials (P<0·05). These results suggest that the combination of coffee intake and repeated bouts of low-intensity exercise enhances fat oxidation in the period after exercise.     

Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO₂) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO₂ similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l^?1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l^?1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO₂ (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.     

Substrate Turnover during Prolonged Exercise in Man: SPLANCHNIC AND LEG METABOLISM OF GLUCOSE, FREE FATTY ACIDS, AND AMINO ACIDS

Arterial concentrations and substrate exchange across the leg and splanchnic vascular beds were determined for glucose, lactate, pyruvate, glycerol, individual acidic and neutral amino acids, and free fatty acids (FFA) in six subjects at rest and during 4 h of exercise at approximately 30% of maximal oxygen uptake. FFA turnover and regional exchange were evaluated using (14)C-labeled oleic acid.The arterial glucose concentration was constant for the first 40 min of exercise, but fell progressively thereafter to levels 30% below basal. The arterial insulin level decreased continuously, while the arterial glucagon concentration had risen fivefold after 4 h of exercise. Uptake of glucose and FFA by the legs was markedly augmented during exercise, the increase in FFA uptake being a consequence of augmented arterial levels rather than increased fractional extraction. As exercise was continued beyond 40 min, the relative contribution of FFA to total oxygen metabolism rose progressively to 62%. In contrast, the contribution from glucose fell from 40% to 30% between 90 and 240 min. Leg output of alanine increased as exercise progressed.Splanchnic glucose production, which rose 100% above basal levels and remained so throughout exercise, exceeded glucose uptake by the legs for the first 40 min but thereafter failed to keep pace with peripheral glucose utilization. Total estimated splanchnic glucose output was 75 g in 4 h, sufficient to deplete approximately 75% of liver glycogen stores. Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol, alanine) had increased 2- to 10-fold after 4 h of exercise, and was sufficient to account for 45% of glucose release at 4 h as compared to 20-25% at rest and at 40 min of exercise. In the case of alanine and lactate, the increase in precursor uptake was a consequence of a rise in splanchnic fractional extraction.It is concluded that during prolonged exercise at a low work intensity (a) blood glucose levels fall because hepatic glucose output fails to keep up with augmented glucose utilization by the exercising legs; (b) a large portion of hepatic glycogen stores is mobilized and an increasing fraction of the splanchnic glucose output is derived from gluconeogenesis; (c) blood-borne substrates in the form of glucose and FFA account for a major part of leg muscle metabolism, the relative contribution from FFA increasing progressively; and (d) augmented secretion of glucagon may play an important role in the metabolic adaptation to prolonged exercise by its stimulatory influence on hepatic glycogenolysis and gluconeogenesis.     

Glucose uptake and binding of digoxin to skeletal muscle

Summary. Physical exercise induces increased uptake of both digoxin and glucose in exercising skeletal muscle. Glucose uptake could be a regulatory factor for the digoxin binding to skeletal muscle, since in dogs, insulin and glucose infusion have been reported to increase the uptake of digoxin in muscle. In the present study on eight healthy digitalized subjects (0·5 mg digoxin daily) the uptake of glucose in skeletal muscle was achieved by infusion of 6 mg/kg body weight/min glucose, 0·004 IE/kg body weight/min insulin and 300 μg/h somatostatin. Serum and skeletal muscle digoxin levels were analysed before and during the infusion. We found no changes in the digoxin levels in serum and skeletal muscle in spite of an increased uptake of glucose in the muscle. Thus, glucose uptake in skeletal muscle is probably not an important regulatory factor for the change in muscle digoxin binding induced by exercise.     

Free Fatty Acid Metabolism of Leg Muscles during Exercise in Patients with Obliterative Iliac and Femoral Artery Disease before and after Reconstructive Surgery

The free fatty acid (FFA) uptake and oxidation and the carbohydrate substrate exchange of leg muscles were studied during exercise in 14 patients with occlusive disease of the iliac or femoral arteries before and 3-6 months after reconstructive vascular surgery and in 5 healthy subjects. ¹⁴C-labeled oleic acid was infused continuously at rest and during exercise at work loads of 150-400 kg-m/min. The arterial concentration of FFA was similar both at rest and during exercise in patients and controls. The patients showed a smaller increase in the fractional turnover of FFA during exercise. Leg uptake and release of FFA in terms of micromoles per liter plasma did not differ significantly either at rest or during exercise between patients and controls. FFA oxidation could not be measured at rest but exercise data showed a lower fractional oxidation of FFA (P < 0.001) in the patient group (53±6%) compared with the controls (84±2%). For the entire material, fractional oxidation of FFA showed a significant negative regression on the lactate/pyruvate ratio in femoral venous blood. The ventilatory respiratory quotient (RQ) and the leg muscle exchange of glucose and lactate in the patients exceeded that of the controls. When six patients were studied after reconstructive surgery, fractional oxidation of FFA had risen from a preoperative value of 47±8 to 90±10%, other data for leg muscle FFA metabolism being unchanged.     

Metabolic adaptations in post-exercise recovery

Summary. To investigate further the hormonal and metabolic adaptations occurring when carbohydrates are ingested after prolonged exercise, we have compared the fate of a 100-g oral glucose load (using ‘naturally labelled’¹³C-glucose) in healthy volunteers after an overnight fast at rest either without previous exercise or after a 3-h exercise performed on a treadmill at about 50% of the individual V?o₂ max. In comparison to the control conditions, the oral glucose tolerance test (OGTT) performed in the post-exercise recovery period was characterized by a greater rise in peripheral blood glucose levels and delayed insulin response. Plasma glucagon values were significantly elevated at the time glucose was given (+48 ±13 pg ml^-1) and at the end of the OGTT. Plasma-free fatty acid (FFA) levels were 1675 ± 103 μEq 1^-1 when glucose was given, and subsequently reduced to values similar to those observed in the control conditions. Indirect calorimetry indicated that OGTT in post-exercise recovery was associated with decreased carbohydrate and increased lipid oxidation when compared to control conditions. Exogenous glucose oxidation was also significantly reduced: 25·1 ± 2·6 vs. 35·9 ± 1·9 g per 7 h. We suggest that the higher plasma glucagon levels and the delayed insulin response played a role in the decreased hepatic glucose retention previously described by others in post-exercise recovery. Our data also suggest that the higher lipid oxidation rate observed at the time glucose was given in the post-exercise period could explain, according to the Randle ‘glucose-fatty acid cycle’, the decreased carbohydrate oxidation and the preferential muscle glycogen repletion already well documented. The reason why the lipid oxidation rate remains increased 3–7 h after glucose ingestion in spite of the fact that FFA levels at that time are similar to those observed in control conditions is still unknown; further kinetic studies are needed to clarify this point.