Non-exercised Muscle Research Articles

‘Direct’ and ‘crossed’ modulation of human motor cortex excitability following exercise

Rapid repetitive movements of the thumb (1 min duration) produce a reversible decrease in the activated primary motor cortex (MI) excitability to transcranial magnetic stimulation (TMS) with recovery within 35–40 min. In the present study we investigated (1) the role of peripheral sensory feedback in inducing such decrease and (2) possible effects of exercise on the non-activated MI. Stimulation of peripheral Ia afferent fibres, induced by 1 min vibration of thenar muscles and 2 Hz electrical stimulation of the median nerve at the wrist, have no effect on motor evoked potential (MEP) amplitude to TMS suggesting no role for sensory feedback to produce MI excitability modulation. Exercise produces a significant ( P < 0.01) decrease of MEPs for homologous non-exercised muscles with concomitant contraction of corresponding motor cortical output maps, suggesting that changes in MI excitability also occur in the non-activated hemisphere. This ‘crossed’ effect might relate to an interhemispheric transfer of information, via homotopic connections of the corpus callosum.

Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise.

The purposes of this study were to assess the presence of 99mTc-labeled white blood cells (WBC) in exercised muscle compared with nonexercised muscle over time and to determine the time course of delayed onset muscle soreness (DOMS) and eccentric torque in 10 female subjects. A pretest was followed by 300 eccentric repetitions of the right quadriceps. DOMS and eccentric torque were measured at 2, 4, 20, 24, 48, and 72 h postexercise. Eccentric torque was also tested at 0 h. Radionuclide images of both quadriceps were taken at 2, 4, 20, and 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle was significantly greater (P < 0.001) than in the nonexercised muscle. Eccentric torque declined at 0 and 24 h postexercise. DOMS peaked at 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle in the first 24 h suggests that acute inflammation occurs as a result of exercise-induced muscle injury. The bimodal pattern of eccentric torque supports the hypothesis that more than one mechanism is involved.

Long-lasting depression of motor-evoked potentials to transcranial magnetic stimulation following exercise.

We used transcranial magnetic stimulation to study the modulation of motor cortex excitability after rapid repetitive movements. Eleven healthy subjects aged 24-32 years were evaluated. Serial motor-evoked potential (MEP) recordings were performed from the right thenar eminence every 5 min for a period of 20 min at rest and for a period of 35 min after repetitive abduction-adduction of the thumb at maximal frequency for 1 min. All subjects presented distinct changes in MEP amplitude after exercise with an approximately 55% mean maximal decrease compared with basal conditions and complete recovery 35 min after the end of the exercise. The time course of MEP amplitude changes presented the following trend: (1) a rapid decrease phase within the first 5 min; (2) a maximal depression phase of 10 min duration (from the 5th to the 15th min); and (3) a slow recovery phase. No significant modifications in post-exercise MEP amplitude were found in ipsilateral non-exercised muscles. In order to determine the level where these changes take place, we recorded the M and F waves induced by median nerve stimulation at the wrist (all subjects) and MEPs in response to transcranial electrical stimulation (five subjects) at rest and during the decrease and maximal depression phases. None of these tests were significantly affected by exercise, indicating that the motor cortex was the site of change. Evaluation of maps of cortical outputs to the target muscle, performed in four subjects, showed an approximately 40% spatial reduction in stimulation sites evoking a motor response during the maximal depression phase. These data prove that exercise induces a reversible, long-standing depression of cortical excitability, probably related to intracortical presynaptic modulation, which transitorily reduces the motor representation area.

The role of body fluid volume and osmolality in thermoregulation and cardiovascular adjustment

Body temperature regulation at rest in a hot environment and/or during exercise requires marked increases in skin blood flow (BF). This is achieved by increasing cardiac output and redistributing BF away from splanchuic, renal, fat and non-exercising muscle tissues, so there is a balance between competing demands for regulation of blood pressure and body temperature. As the heat load increases, central venous pressure (CVP) decreases due to reduced central blood volume brought about by the above increase in peripheral blood volume and by reduced total blood volume due to sweat loss. Skin BF becomes sub-maximal, purportedly due to the falling CVP acting via low-pressure baroreceptors in a feed-forward manner to minimise changes in arterial pressure. That is, the thermoregulatory demands become so great that disturbance of cardiovascular function becomes intolerable. Therefore, there is a conflict in which cardiovascular control ultimately dominates body temperature control to the extent that the rising core temperature is aggravated by reductions in sweating and in skin BF and volume. An important role may also be played by endotoxaemia due to the high temperature and low gastrointestinal BF allowing increased quantities of lipepolysaccharide to cross from the gastrointestinal lumen; this could act as in fever to inhibit heat loss and increase heat production. 'Collapse' occurs due to CNS or other secondary non-cardiovascular effects of the severe hyperthermia etythrocyte sphering and disseminated intravascular coagulation result in microthrombosns and coagulative necrosis in nervous and other tissues, leading to death. The concept of an adjustable critical thermal maximum may explain the apparent association of 'physiological failure' with widely varying levels of body temperature during severe heat stress.

Correlation between fructose 2,6-bisphosphate and lactate production in skeletal muscle

The epinephrine-induced production of lactate in nonexercising muscles may be due in part to allosteric activation of 6-phosphofructo-1-kinase by fructose 2,6-bisphosphate (F-2,6-P2). To determine if a correlation exists between F-2,6-P2 and lactate production in skeletal muscle, isolated rat hindlimbs were perfused for 30 min with a medium containing epinephrine at concentrations varying between 1.7 +/- 0.5 and 72.4 +/- 4.2 nM. In comparison to control values, hindlimbs perfused with 72.4 +/- 4.2 nM epinephrine had a two- to threefold increase in F-2,6-P2 and a fourfold increase in muscle lactate production. Hindlimb lactate production was highly correlated to gastrocnemius adenosine 3',5'-cyclic monophosphate (r = 0.80), fructose 6-phosphate (r = 0.87), and F-2,6-P2 (r = 0.81). The adenosine 3',5'-cyclic monophosphate-mediated increase in glycogenolysis with consequent increase in fructose 6-phosphate (substrate for 6-phosphofructo-1-kinase and 6-phosphofructo-2-kinase) is likely important for induction of lactate production by inactive muscle. The high correlation between muscle F-2,6-P2 and muscle lactate production at varying concentrations of epinephrine supports the hypothesis that the epinephrine-induced activation of glycolysis and lactate production in nonexercising muscle is mediated in part by increases in F-2,6-P2 levels.

Progression of venoconstriction in patients after heart transplantation during exercise

Changes of both central hemodynamics and peripheral circulation in non-exercising muscle were investigated in 17 patients after successful orthotopic heart transplantation during moderate supine isotonic leg-exercise. Changes of peripheral circulation were measured in 14 healthy controls. The cardiac output rose from 5.71 to 9.45 l/min, the right atrial pressure from 3.5 to 12 mmHg, mean pulmonary arterial pressure from 17.4 to 36.9 mmHg, and pulmonary capillary wedger pressure from 9.5 to 23.5 mmHg. Venoconstriction, already present in the rest in patients after heart transplantation, further increased during the exercise (venous compliance lowered from 0.0454 to 0.0309 ml/mmHg). In controls no changes were observed (venous compliance being 0.0833 at rest and 0.0839 ml/mmHg during exercise). Negative correlation was found between an increase in pulmonary arterial pressure and a decrease in venous compliance. The authors hypothesise that venoconstriction could serve to increase of cardiac output via Frank-Starling mechanisms in patients after heart transplantation. Forearm blood flow during the exercise decreased (from 3.4 to 2.0 ml/100 ml/min), while local peripheral resistance rose (from 35.9 to 78.8 units) in patients after heart transplantation. These changes were not observed in controls.

Effects of exercise and glycogen depletion on glyconeogenesis in muscle

In the present study, we investigated the hypotheses that 1) skeletal muscle glyconeogenesis will increase after exercise, 2) greater changes in glyconeogenesis will be observed after exercise in fast-twitch muscles than in slow-twitch muscles, and 3) glycogen repletion will reduce the rates of glyconeogenesis. Mouse soleus and extensor digitorum longus (EDL) glycogen depots were reduced to the same levels by treadmill exercise (60 min) or epinephrine injection (75 micrograms/100 g body wt ip). Untreated animals were used as controls. We were able to prevent glycogen repletion by incubating muscles in vitro with sorbitol (75 mM) and to increase glycogen concentrations in vitro by incubating muscles with glucose (75 mM). The experimental results showed that glyconeogenesis was increased by exercise (EDL, +51%; soleus, +82%) when glycogen levels were kept low. When glycogen depots were increased, the rate of glyconeogenesis was lowered in the exercised EDL (P < 0.05) but not in the soleus (P > 0.05). Reductions in muscle glycogen by epinephrine did not change the rate of glyconeogenesis in EDL, either when glycogen depots were kept low or were repleted (P > 0.05). In contrast, in the soleus, epinephrine-induced reductions in glycogen did stimulate glyconeogenesis (P < 0.05). Analyses in EDL showed that in nonexercised muscles glycogen concentrations were minimally effective in altering the rates of glyconeogenesis. A 30% decrement in glycogen increased glyconeogenesis by 5% in resting muscles, whereas the same decrement increased glyconeogenesis by 51% in exercised muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle vascular responses in human limbs to isometric handgrip

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.

Effects of exercise on insulin sensitivity in humans.

Physical exercise is promoted as one of the primary therapeutic strategies available to increase insulin sensitivity in individuals deemed at risk from insulin resistance and its attendant hyperinsulinism. Subjects with non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) represent the major clinical population in which physical training is promoted as a treatment modality to improve insulin sensitivity. This manuscript reviews both the acute effects of muscular contractions and the effects of physical training on insulin sensitivity in NIDDM and insulin-dependent diabetic (IDDM) human subjects. Additionally, the effects of localized (regional) muscular contractions on insulin-mediated glucose disposal in previously exercised and nonexercised muscle groups will be discussed briefly.

Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle.

1. The functional properties of tibialis anterior muscles of normal adult (C57BL/10) and age-matched dystrophin-deficient (C57BL/10 mdx) mice have been investigated in situ. Comparisons were made between tibialis anterior muscle strength, rates of force development and relaxation, force-frequency responses and fatiguability. Subjecting mdx and C57 muscles to a regimen of eccentric exercise allowed the hypothesis to be tested that dystrophin-deficient muscles are more susceptible to exercise-induced muscle damage. 2. mdx muscles were, on average, 30% stronger than C57 muscles and almost 80% heavier, but both had similar muscle lengths. Thus, although mdx muscles were stronger in absolute terms, their estimated force per unit cross-sectional area was significantly less than that of C57 muscles. 3. The force-frequency relationships of C57 and mdx muscles differed in that whilst, at 40 Hz, the former developed 70% of the force developed at 100 Hz, the latter developed only 55% of the maximal force. Twitch force was normal in mdx muscles, but contraction time was shortened, and the consequent reduction in fusion frequency probably explains the force-frequency differences observed between the two groups. 4. mdx muscles were less fatiguable than normal muscles when stimulated repeatedly at a frequency of 40 Hz. It is possible that the lower relative force at 40 Hz in mdx muscles entailed a lower energy demand and thus a slower rate of fatigue than seen in normal muscles. 5. Eccentrically exercised C57 muscles showed a large loss of maximal force for up to 12 days after exercise. Maximal force loss occurred 3 days after exercise (55% of non-exercised tibialis anterior muscle), which also corresponded with the period of greatest fibre necrosis. C57 muscles showed a significantly reduced 40 Hz/100 Hz force-frequency ratio at 1 and 3 days after exercise. This was primarily due to a reduced twitch amplitude rather than to a change in the time course of the twitch. It is unlikely, therefore, that the altered contractile characteristics of mdx muscle were a result of the presence of damaged but otherwise normal fibres. 6. C57 and mdx tibialis anterior muscles displayed similar degrees of force loss after exercise. Furthermore, the rate of recovery after the nadir of force loss was very similar for the two groups. By 12 days after exercise, force recovered to 76% and 80% of control in C57 and mdx muscles, respectively. Our findings do not support the hypothesis that dystrophin-deficient muscle is more susceptible to exercise-induced muscle damage.

Increased glucose transport in nonexercising muscle

Changes in blood flow and muscle glycogen in nonexercising muscle during exercise suggest that glucose transport may be increased in nonexercising muscles. Therefore, we compared 3-O-methyl-D-glucose (3-MG) transport in exercised and nonexercised perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius), in the absence and presence of insulin (30 nM). Specifically, the following four treatments were used: 1) normal rest, 2) normal exercise animals (90 min running 15 m/min, 8% grade), 3) hindlimb-suspended animals at rest (90 min), and 4) hindlimb-suspended animals while exercising on the forelimbs (90 min running 15 m/min, 8% grade). In separate groups of animals, it was shown from the analyses of the electromyographic interference patterns that muscle activity was sharply reduced in hindlimb-suspended muscles both at rest and during exercise (soleus and plantaris). Glycogen decrements were also observed in nonexercising muscles during exercise (soleus, plantaris, and red gastrocnemius; P less than 0.05), although these decrements were less than in the exercised muscles (P less than 0.05). Glucose transport differed among muscles (soleus = plantaris greater than red gastrocnemius greater than white gastrocnemius), and typical increments were observed after exercise (P less than 0.05) and with insulin stimulation (P less than 0.05). An additive effect of insulin and exercise was also observed (P less than 0.05). In nonexercised muscles with no insulin in the perfusate, an increase in 3-MG transport occurred (P less than 0.05). In the presence of insulin, an increase in 3-MG transport was also observed in the nonexercised red and white gastrocnemius muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Glyconeogenic and oxidative lactate utilization in skeletal muscle.

In this article we present a synthesis of recent information concerning the fate of lactate in skeletal muscle. This is important since lactate is continuously produced by skeletal muscle at rest and at all levels of exercise. Therefore, the disposal of lactate as an 'intermediary' metabolite is discussed. The two primary fates of lactate in skeletal muscle are (1) oxidation and (2) glycogen synthesis (glyconeogenesis). From recent evidence it seems relatively clear that glycogen formation in muscle is primarily dependent on glucose, although in fast twitch muscles a considerable proportion of lactate can account for muscle glycogen formation, especially immediately after exercise when circulating lactate levels are elevated. Exactly how lactate is converted to glycogen is not known yet, but an extramitochondrial pathway that is divergent from the hepatic gluconeogenic pathway seems likely. Oxidation of lactate is quantitatively the most important means of disposing of lactate, whether in exercising or nonexercising muscle. The lactate gradient between muscle and blood may be an important factor dictating whether lactate is taken up or released by muscle, independent of whether the muscle is active or not. Finally a novel role for epinephrine is considered that may be important for the mitochondrial oxidation of lactate.

Non-exercising muscle metabolism during exercise

Glycogen decrements have been observed in non-exercising muscles during exercise. We therefore investigated whether the degraded glycogen was retained within the muscle in the form of glycolytic intermediates, or whether it was effluxed from the non-exercising muscles. For these studies a suspension harness was used to unload the hindlimb muscles at rest and during exercise [McDermott et al. (1987) J Appl Physiol 63:1275-1283]. Concentrations of glycogen and glycolytic intermediates glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, glycerol 3-phosphate, and lactate) were measured in non-exercising and exercising muscles (soleus, plantaris, red and white gastrocnemius) during a 90-min exercise about 15 m/min, 8% grade). On-line electromyographic analysis showed that the contractile activity in the non-exercising muscles was markedly lower than in the exercising muscles. Similar decrements in muscle glycogen levels were observed in both the non-exercising and exercising muscles at the end of the 90-min, exercise bout (P less than 0.05), despite significantly different activity profiles. An increase in tissue lactate concentrations occurred in both non-exercising and exercising muscle (P less than 0.05), although only slight changes in the glycolytic intermediates occurred. The sum total of all the accumulated glycolytic intermediates and lactate (converted to glucosyl units) in the non-exercising muscles only accounted for a small fraction of the glycogen degraded (approximately 15%-28%). We conclude that the metabolism of glycogen is enhanced in non-exercising muscle, and that glycogen utilization is uncoupled from the energetic demands of the muscle. Furthermore, the glycogen mobilized in non-exercising muscle is not retained within the muscle in other metabolite pools.(ABSTRACT TRUNCATED AT 250 WORDS)

Divergence of muscle and liver fructose 2,6-diphosphate in fasted exercising rats

Previous studies demonstrate that nonexercising muscle may serve as a source of lactate for hepatic gluconeogenesis during long-term exercise. The concentration of fructose 2,6-diphosphate (F-2,6-P2), a signal molecule that accelerates glycolysis, was examined in liver and muscles of fed and fasted resting rats and in fasted rats run for 5, 15, or 30 min at 21 m/min (15% grade). Liver F-2,6-P2 decreased in response to fasting and exercise. White quadriceps (composed predominantly of type IIb fibers) F-2,6-P2 increased from 2.2 +/- 0.1 to 4.5 +/- 0.4 pmol/mg in the fasted rats in response to 30 min of treadmill running. No increase was observed in the red region of the quadriceps (composed of type IIa fibers). The fasted rats also exhibited a threefold increase in glucose 1,6-diphosphate (G-1,6-P2) in the white quadriceps after 30 min of exercise, whereas no significant changes were observed in the red quadriceps or in liver. The increases in F-2,6-P2 and G-1,6-P2 may be important in accelerating glycolysis and enhancing lactate production in muscles that are not glycogen depleted during long-term exercise.

Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle

The effect of 10 wk endurance swim training on 3-O-methylglucose (3-MG) uptake (at 40 mM 3-MG) in skeletal muscle was studied in the perfused rat hindquarter. Training resulted in an increase of approximately 33% for maximum insulin-stimulated 3-MG transport in fast-twitch red fibers and an increase of approximately 33% for contraction-stimulated transport in slow-twitch red fibers compared with nonexercised sedentary muscle. A fully additive effect of insulin and contractions was observed both in trained and untrained muscle. Compared with transport in control rats subjected to an almost exhaustive single exercise session the day before experiment both maximum insulin- and contraction-stimulated transport rates were increased in all muscle types in trained rats. Accordingly, the increased glucose transport capacity in trained muscle was not due to a residual effect of the last training session. Half-times for reversal of contraction-induced glucose transport were similar in trained and untrained muscles. The concentrations of mRNA for GLUT-1 (the erythrocyte-brain-Hep G2 glucose transporter) and GLUT-4 (the adipocyte-muscle glucose transporter) were increased approximately twofold by training in fast-twitch red muscle fibers. In parallel to this, Western blot demonstrated a approximately 47% increase in GLUT-1 protein and a approximately 31% increase in GLUT-4 protein. This indicates that the increases in maximum velocity for 3-MG transport in trained muscle is due to an increased number of glucose transporters.

A model for nonexercising hindlimb muscles in exercising animals

Nonexercising muscles appear to be metabolically active during exercise. Animal models for this purpose have not been established. However, we have been able to teach animals to run on their forelimbs while their hindlimbs are suspended above the treadmill with no visible limb movement. To document that indeed this mode of exercise does not provoke additional muscle activity, we have compared the levels of neural activation of the soleus and plantaris muscles using a computer analysis of the electromyographic interference pattern, recorded from bipolar fine wire electrodes implanted across each muscle. Via computer analyses of the electromyographic interference patterns the frequencies and amplitudes of motor unit action potentials were obtained. The data were sampled during 20 s of every minute of observation. Comparisons were made in four conditions: (i) resting on the treadmill while bearing weight on the hindlimbs (normal rest), (ii) running on the treadmill (15 m/min, 8% grade) on all four limbs (normal exercise), (iii) resting while the hindlimbs were suspended in a harness above the treadmill (suspended rest), and (iv) exercising with the forelimbs (15 m/min, 8% grade) while the hindlimbs were suspended above the treadmill (suspended exercise). All four experimental conditions were carried out for 90 min each and were performed by each animal. The results clearly show that muscle activities (frequencies and amplitudes), when the hindlimbs are suspended above the treadmill, at rest or during exercise, are lower than the activities in these same muscles when the animals are at rest, supporting only their body weight. Activities in the same muscles during exercise were from 300 to 2000% greater than during hindlimb suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acid metabolism after intense exercise

We studied postexercise amino acid metabolism, in the whole body and across the forearm. Seven volunteers were infused with L-[alpha-15N]lysine and L-[1-13C]-leucine twice [one time during 3 h after cycle exercise (75% VO2max), and one time in the resting state]. Whole body protein breakdown was estimated from dilution of L-[alpha-15N]lysine and L-[1-13C]ketoisocaproic acid (KIC) enrichments in plasma. Leucine oxidation was calculated from 13CO2 enrichments in expired air. Whole body protein breakdown was not increased above resting levels during the recovery period. Leucine oxidation was decreased after exercise (postexercise 13 +/- 2.3 vs. resting 19 +/- 3.2 mumol.kg-1.h-1; P less than 0.02), while nonoxidative leucine disposal was increased (115 +/- 6.1 vs. 103 +/- 5.6 micrograms.kg-1.min-1; P less than 0.02). After exercise, forearm net lysine balance was unchanged (87 +/- 25 vs. 93 +/- 28 nmol.100 ml-1.min-1), but there were decreases in forearm muscle protein degradation (219 +/- 51 vs. 356 +/- 85 nmol.100 ml-1.min-1; P less than 0.05) and synthesis (132 +/- 41 vs. 255 +/- 69 nmol.100 ml-1.min-1; P less than 0.01). In conclusion, after exercise 1) whole body protein degradation is not increased, 2) leucine disposal is directed away from oxidative and toward nonoxidative pathways, 3) forearm protein synthesis is decreased. Postexercise increases in whole body protein synthesis occur in tissues other than nonexercised muscle.

Carbohydrate metabolism in skeletal muscle: an update of current concepts.

We have reviewed carbohydrate metabolism in skeletal muscle with an emphasis on recent information. In this review a significant number of points have been made. These are summarized below. 1. CP and glycogen are concomitantly metabolized during short-term (less than or equal to 10 s) intense exercise. 2. Both epinephrine and contractile activity regulate glycogen use in muscle. 3. Glycogen sparing during exercise is promoted by fatty acids and probably glucose. 4. Glycogenesis increases during exercise in exercising muscle. 5. Ingested glucose is easily metabolized during exercise. 6. The heterogeneity in glucose uptake among muscles at rest and during exercise is likely not caused by blood flow differences per se. 7. Insulin binding, glucose transporters, glucose uptake, and glycogenesis are greater in ST than in FT muscles. 8. Acute changes in glucose metabolism are not always attributable to concomitant changes in insulin binding to its receptor. 9. Contractile activity alone will increase glucose uptake in muscle, and insulin is not required. 10. Insulin and contractile effects on glucose uptake are additive, suggesting that these stimuli mobilize different pools of glucose transporters. 11. Glycogen loss occurs in exercising and non-exercising muscle; therefore this substrate is not an appropriate index of muscle contractile activity. 12. Carbohydrate mobilization does not appear to be strictly determined by need for this substrate nor by the rate of muscle metabolism. 13. Glyconeogenesis from lactate occurs in ST and FT muscles and is regulated by pH.

Reflex stimulation of sympathetic outflow during rhythmic exercise in humans

The aim of this study was to determine whether a chemically generated reflex arising in nonischemic skeletal muscle normally increases sympathetic outflow during rhythmic exercise. To accomplish this aim, we recorded muscle sympathetic nerve activity (MSNA, peroneal nerve) in conscious humans during exercise interventions designed to alter the relationship between muscle blood flow and metabolic demand. Under normal conditions, MSNA increased during moderate but not during mild levels of rhythmic handgrip (0.67 Hz) and one-arm cycling (0.83 Hz). MSNA remained elevated when the moderate level of rhythmic handgrip was followed by forearm vascular occlusion, a maneuver that sustains muscle chemoreflex stimulation. Complete arm vascular occlusion was needed to increase MSNA during mild arm cycling, whereas even partial vascular occlusion greatly amplified the stimulation of MSNA normally produced by the moderate level of arm cycling. We conclude that a chemically generated reflex arising in nonischemic working muscle plays an important role in the normal activation of sympathetic discharge to nonexercising leg muscles during moderate but not during mild levels of rhythmic arm exercise.

Effects of insulin and exercise on muscle lipoprotein lipase activity in man and its relation to insulin action.

The effects of exercise and a physiological increase in plasma insulin concentration on muscle lipoprotein lipase activity (mLPLA), leg exchange of glucose, and serum lipoprotein levels were investigated in healthy young men. During euglycemic hyperinsulinemia (n = 7) at 44 mU.liter-1, m-LPLA in non-exercised muscle decreased from 30 +/- 7.4 mU.g-1 wet weight (w.w.) (mean +/- SE) to 19 +/- 3.3 (P less than 0.05). Furthermore, the decrease in m-LPLA correlated closely (r = 0.97, P less than 0.05) with the increase in leg glucose uptake. Moreover, basal m-LPLA correlated with the insulin-induced increase in leg glucose uptake (r = 0.93, P less than 0.05). In the control group (n = 6) in which saline was infused in place of insulin and glucose, m-LPLA in nonexercised muscle did not change with time. No change in m-LPLA was observed immediately after one-legged knee extension exercise, but 4 h after exercise m-LPLA was higher (P less than 0.05) in the exercised thigh (47 +/- 17.8 mU.g-1 w.w.) compared with the contralateral nonexercised thigh (29 +/- 6.3 mU.g-1 w.w.). This difference was not found 8 h after exercise. The triacylglycerol content of serum lipoproteins decreased during insulin infusion. It is concluded that in contrast to the effect on adipose tissue, physiological concentrations of insulin decrease m-LPLA in proportion to the effect of insulin on muscle glucose uptake, while muscle contractions cause a local, delayed, and transient increase in m-LPLA. Further-more, basal m-LPLA is an indicator of muscle insulin sensitivity.