Exercise training increases glucose transporter protein GLUT-4 in skeletal muscle of obese Zucker (fa/fa) rats

The present study examined the level of GLUT-4 glucose transporter protein in gastrocnemius muscles of 36 week old genetically obese Zucker (fa/fa) rats and their lean (Fa/-) littermates, and in obese Zucker rats following 18 or 30 weeks of treadmill exercise training. Despite skeletal muscle insulin resistance, the level of GLUT-4 glucose transporter protein was similar in lean and obese Zucker rats. In contrast, exercise training increased GLUT-4 protein levels by 1.7 and 2.3 fold above sedentary obese rats. These findings suggest endurance training stimulates expression of skeletal muscle GLUT-4 protein which may be responsible for the previously observed increase in insulin sensitivity with training.     

Fiber type composition and enzyme activities of muscles in two models of obese rats

• 1.1. In oxidative (soleus) and glycolytic (extensor digitorum longus) muscles of obese Zucker rats, a significant decrease in the percentage of relative area occupied by glycolytic fibers was observed.
• 2.2. The activity of citrate synthase and β-hydroxy-acyl-CoA-dehydrogenase was significantly higher in muscles of obese than of lean Zucker rats.
• 3.3. In rats, 6 weeks after lesion of the ventromedial hypothalamus, no changes were observed.
• 4.4. This indicates that neither the proportion of oxidative fibers, nor the oxidative capacities are decreased in skeletal muscles of obese rats suggesting that insulin resistance cannot be ascribed to a higher glycolytic-oxidative fiber ratio.

     

Exercise training restores decreased cellular immune functions in obese Zucker rats

Moriguchi, S., M. Kato, K. Sakai, S. Yamamoto, and E. Shimizu. Exercise training restores decreased cellular immune functions in obese Zucker rats. J. Appl.Physiol. 84(1): 311-317, 1998.This studyinvestigated whether exercise training had a beneficial effect on thedecreased mitogen response and improved a decreased expression ofglucose transporter 1 (GLUT-1) in splenocytes from obese Zucker rats.Experimental groups were lean and sedentary and exercise-trained obeseZucker rats. Exercise training, running on a motor-driven treadmill for5 days/wk for 40 wk, did not induce a significant decrease in bodyweight in obese Zucker rats. The plasma insulin concentration, showinga significant increase compared with lean Zucker rats, was unaffectedby exercise training. However, the plasma triglyceride concentration inobese Zucker rats was significantly depressed by exercise training,whereas it was still higher than that in lean Zucker rats. In addition,natural killer cell activity and concanavalin A-induced mitogenesis ofsplenic lymphocytes of obese Zucker rats were significantly restored. In these splenic lymphocytes, glucose uptake was significantly lowercompared with that in lean Zucker rats, which was also improved byexercise training. Although the expression of GLUT-1, the major glucosetransporter in immune cells, was depressed in splenic lymphocytes ofobese Zucker rats, exercise training induced a significant improvement.These results suggest that exercise training has a beneficial effect onthe decreased cellular immune functions in obese Zucker rats, which isassociated, in part, with the improvement in GLUT-1 expression.

     

Endurance training increases lactate transport in male Zucker fa/fa rats

The purpose of this study was to investigate the effect of endurance training (10 weeks) on previously reported alterations of lactate exchange in obese Zucker fa/fa rats. We used sarcolemmal vesicles to measure lactate transport capacity in control sedentary rats, Zucker (fa/fa), and endurance trained Zucker (fa/fa) rats. Monocarboxylate transporter (MCT) 1 and 4 content was measured in sarcolemmal vesicles and skeletal muscle. Training increased citrate synthase activity in soleus and in red tibialis anterior, and improved insulin sensitivity measured by intraperitoneal glucose tolerance test. Endurance training increased lactate influx in sarcolemmal vesicles at 1 mM of external lactate concentration and increased MCT1 expression on sarcolemmal vesicles. Furthermore, muscular lactate level was significantly decreased after training in red tibialis anterior and extensor digitorum longus. This study shows that endurance training improves impairment of lactate transport capacity that is found in insulin resistance state like obesity and type 2 diabetes.     

Insulin resistance in soleus muscle from obese Zucker rats. Involvement of several defective sites

1. The effect of insulin upon glucose transport and metabolism in soleus muscles of genetically obese (fa/fa) and heterozygote lean Zucker rats was investigated at 5–6 weeks and 10–11 weeks of age. Weight-standardized strips of soleus muscles were used rather than the intact muscle in order to circumvent problems of diffusion of substrates. 2. In younger obese rats (5–6 weeks), plasma concentrations of immunoreactive insulin were twice those of controls, whereas their circulating triacylglycerol concentrations were normal. Insulin effects upon 2-deoxyglucose uptake and glucose metabolism by soleus muscles of these rats were characterized by both a decreased sensitivity and a decrease in the maximal response of this tissue to the hormone. 3. In older obese rats (10–11 weeks), circulating concentrations of insulin and triacylglycerols were both abnormally elevated. A decrease of 25–35% in insulin-binding capacity to muscles of obese rats was observed. The soleus muscles from the older obese animals also displayed decreased sensitivity and maximal response to insulin. However, at a low insulin concentration (0.1m-i.u./ml), 2-deoxyglucose uptake by muscles of older obese rats was stimulated, but such a concentration was ineffective in stimulating glucose incorporation into glycogen, and glucose metabolism by glycolysis. 4. Endogenous lipid utilization by muscle was calculated from the measurements of O₂ consumption, and glucose oxidation to CO₂. The rate of utilization of fatty acids was normal in muscles of younger obese animals, but increased in those of the older obese rats. Increased basal concentrations of citrate, glucose 6-phosphate and glycogen were found in muscles of older obese rats and may reflect intracellular inhibition of glucose metabolism as a result of increased lipid utilization. 5. Thus several abnormalities are responsible for insulin resistance of muscles from obese Zucker rats among which we have observed decreased insulin binding, decreased glucose transport and increased utilization of endogenous fatty acid which could inhibit glucose utilization.     

Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat

Asp, Sven, Allan Watkinson, Nicholas D. Oakes, and Edward W. Kraegen. Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat.J. Appl. Physiol. 82(4):1327-1332, 1997.Our aim was to examine the effect of prioreccentric contractions on insulin action locally in muscle in theintact conscious rat. Anesthetized rats performed one-leg eccentriccontractions through the use of calf muscle electrical stimulationfollowed by stretch of the active muscles. Two days later, basal andeuglycemic clamp studies were conducted with the rats in the awakefasted state. Muscle glucose metabolism was estimated from2-[¹⁴C(U)]deoxy-D-glucoseandD-[3-³H]glucose administration, and comparisons were made between the eccentrically stimulated and nonstimulated (control) calfmuscles. At midphysiological insulin levels, effects ofprior eccentric exercise on muscle glucose uptake were notstatistically significant. Maximal insulin stimulation revealed reducedincremental glucose uptake above basal(P < 0.05 in the red gastrocnemius;P < 0.1 in the white gastrocnemiusand soleus) and impaired net glycogen synthesis in all eccentricallystimulated muscles (P < 0.05). Weconclude that prior eccentric contractions impair maximal insulin action (responsiveness) on local muscle glucose uptake and glycogen synthesis in the conscious rat.

     

Contractile function and low-intensity exercise effects of old dystrophic (mdx) mice

Oldmdx mice display a severe myopathyalmost identical to Duchenne's muscular dystrophy. This study examinedthe contractile properties of old mdxmuscles and investigated any effects of low-intensity exercise.Isometric contractile properties of the extensor digitorum longus (EDL)and soleus muscles were tested in adult (8-10 mo) and old (24 mo,split into sedentary and exercised groups)mdx mice. The EDL and soleus from oldmdx mice exhibited decreased absolutetwitch and tetanic forces, and the soleus exhibited a >50% decreasein relative forces (13.4 ± 0.4 vs. 6.0 ± 0.9 N/cm²) compared with adult mice.Old mdx muscles also showed longer contraction times and a higher percentage of type I fibers. Normal andmdx mice completed 10 wk of swimming,but mdx mice spent significantly lesstime swimming than normal animals (7.8 ± 0.4 vs. 15.8 ± 1.1 min, respectively). However, despite their severe dystrophy,mdx muscles responded positively tothe low-intensity exercise. Relative tetanic tensions were increased(~25% and ~45% for the EDL and soleus, respectively) after theswimming, although absolute forces were unaffected. Thus these resultsindicate that, even with a dystrophin-deficient myopathy,mdx muscles can still respond to low-intensity exercise. This study shows that the contractile functionof muscles of old mdx mice displaysmany similarities to that of human dystrophic patients and providesfurther evidence that the use of non-weight-bearing, low-intensityexercises, such as swimming, has no detrimental effect on dystrophicmuscle and could be a useful therapeutic aid for sufferers of musculardystrophy.

     

Changes of action potentials and force at lowered [Na+]o in mouse skeletal muscle: implications for fatigue

We examined 1) whether the effects of lowered trans-sarcolemmal Na⁺ gradient on force differed between nonfatigued fast- and slow-twitch muscles of mice and 2) whether effects on action potentials could explain the decrease of force. The Na⁺ gradient was reduced by lowering the extracellular [Na⁺] ([Na⁺]_o). The peak force-[Na⁺]_o relationships for the twitch and tetanus were the same in nonfatigued extensor digitorum longus and soleus muscles: force was maintained over a large range of [Na⁺]_o and then decreased abruptly over a much smaller range. However, fatigue was significantly exacerbated at a lowered [Na⁺]_o that had little effect in nonfatigued soleus muscle. This finding suggests that substantial differences exist in the Na⁺ effect on force between nonfatigued and fatigued muscle. The reduced contractility in nonfatigued muscles at lowered [Na⁺]_o was largely due to 1) an increased number of inexcitable fibers and threshold for action potentials, 2) a reduction of action potential amplitude, and 3) a reduced capacity to generate action potentials throughout trains. sodium gradient; muscle contraction; action potential train; extensor digitorum longus; soleus     

Exercise training and the glucose transport system in obese SHHF/Mcc-facp rats

Ferrara, Cynthia M., W. Michael Sherman, Nicole Leenders,Sylvia A. McCune, and Karla Roehrig. Exercise training and theglucose transport system in obeseSHHF/Mcc-fa^cprats. J. Appl. Physiol. 81(4):1670-1676, 1996.The effects of a similar exercise trainingstimulus on maximal insulin-stimulated (MIS) plasma membrane glucosetransporter number and glucose transport were determined in lean andobeseSHHF/Mcc-fa^cprats. Six-week-old lean and obese male rats were randomly divided intofour groups: lean sedentary (LSed), obese sedentary (OSed), leanexercise (LEx), and obese exercise (OEx). An 8- to 12-wk treadmillrunning program equalized daily muscular work for LEx and OEx. Plasmamembranes were isolated from control and MIS muscles of mixed fibertypes. MIS significantly increased glucose transport (3.4- and2.8-fold) in LSed and OSed, respectively. MIS significantly increased glucose transporter number (2.5-fold) in LSed, but there wasno increase in glucose transporter number in OSed. Peak oxygen uptakeand citrate synthase activity were increased a similar amount for LExand OEx groups, demonstrating a similar training stimulus. MISsignificantly and similarly increased glucose transport in LEx and OEx(4.4- and 5.1-fold, respectively). The effects of MIS on plasmamembrane glucose transporter number in the exercise-trained rats weresimilar to the responses observed in the sedentary lean and obesegroups. MIS significantly increased glucose transporter number(2.6-fold) in LEx, whereas there was no increase in glucose transporternumber in OEx. The reduction in MIS glucose transport in OSed appearsto be related to a defect in the processes associated with thetranslocation of glucose transporters to the plasma membrane. Exercisetraining of the obese rats apparently did not alter this defect.Similar increases in peak oxygen uptake, citrate synthase, and MISglucose transport in LEx and OEx groups suggest that insulin resistancedoes not limit the ability of the glucose transport system to adapt toexercise training in the obese maleSHHF/Mcc-fa^cprats.

     

Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat.

1. Rats were treated with dexamethasone for 4 days before measurement of the rates of lactate formation [which is an index of hexose transport; see Challiss, Lozeman, Leighton & Newsholme (1986) Biochem. J. 233, 377-381] and glycogen synthesis in response to various concentrations of insulin in isolated incubated soleus and extensor digitorum longus muscle preparations. 2. The concentration of insulin required to stimulate these processes half-maximally in soleus and extensor digitorum longus muscles isolated from control rats was about 100 muunits/ml. 3. Dexamethasone increases the concentration of insulin required to stimulate glycolysis half-maximally in soleus and extensor digitorum longus preparations to 250 and 300 muunits/ml respectively. The respective insulin concentrations necessary to stimulate glycogen synthesis half-maximally were about 430 and 370 muunits/ml for soleus and extensor digitorum longus muscle preparations isolated from steroid-treated rats. 5. Dexamethasone treatment did not change the amount of insulin bound to soleus muscle.     

UCP3 gene expression does not correlate with muscle oxidation rates in troglitazone-treated Zucker fatty rats

Uncoupling protein-3 (UCP3), a mitochondrial carrier protein predominantly expressed in muscle, has been suggested to release stored energy as heat. The insulin-sensitizing thiazolidinediones enhance glucose disposal in skeletal muscle and have been reported to increase the expression of uncoupling proteins in various experimental systems. We therefore studied the effect of troglitazone treatment on UCP3 gene expression in muscles from lean and obese Zucker rats. In comparison with obese littermates, basal UCP3 mRNA levels in lean Zucker rats tended to be higher in white and red gastrocnemius muscles, but were lower in soleus (P<0.001) muscle and heart (P<0.01). In lean rats, troglitazone significantly increased UCP3 gene expression in white and red gastrocnemius and heart muscles (all P<0.01). In contrast, the drug reduced UCP3 mRNA expression in red gastrocnemius and soleus muscles of obese littermates (all P<0.001). The troglitazone-dependent decrease in UCP3 gene expression was accompanied by an increased weight gain in obese rats, while no such effect was observed in lean rats. In obese rats, improvement of insulin resistance by troglitazone was associated with increased rates of basal and insulin-stimulated CO(2) production from glucose measured in soleus muscle. These studies demonstrate that effects of troglitazone on UCP3 gene expression depend on the phenotype of Zucker rats and that troglitazone-induced metabolic improvements are not related to increased uncoupling resulting from upregulation of UCP3 mRNA expression in muscle.     

Perturbations of the stress-induced GLUT4 localization pathway in slow-twitch muscles of obese Zucker rats

Past studies have suggested that the stress-induced GLUT4 localization pathway is damaged in fast-twitch muscles (white muscles) of obese subjects. In this study, we used obese rodents in an attempt to determine whether the stress-induced GLUT4 localization pathway is abnormal in slow-twitch muscles (red muscles), which are responsible for most daily activities. Protein expression levels of the intracellular stress sensor AMP-activated protein kinase (AMPK), its upstream kinase LKB1, its downstream protein AS160 and the glucose transporter protein 4 (GLUT4) in the red gastrocnemius muscle were measured under either resting or stress conditions (1 h of swimming or 14% hypoxia) in both lean and obese Zucker rats (n = 7 for each group). At rest, obese rats displayed higher fasting plasma insulin levels and increased muscle AMPK and AS160 phosphorylation levels compared with lean controls. No significant difference was found in the protein levels of LKB1, total GLUT4, or membrane GLUT4 between the obese and lean control groups. After one hour of swimming, AMPK and AS160 phosphorylation levels and the amount of GLUT4 translocated to the plasma membrane were significantly elevated in lean rats but remained unchanged in obese rats relative to their resting conditions. One hour 14% hypoxia did not cause significant changes in the LKB1-AMPK-AS160-GLUT4 pathway in either lean or obese rats. This study demonstrated that the AMPK-AS160-GLUT4 pathway was altered at basal levels and after exercise stimulation in the slow-twitch muscle of obese Zucker rats.     

Evidence that nitric oxide increases glucose transport in skeletal muscle

Balon, Thomas W., and Jerry L. Nadler. Evidence thatnitric oxide increases glucose transport in skeletal muscle.J. Appl. Physiol. 82(1): 359-363, 1997.Nitric oxide synthase (NOS) is expressed in skeletal muscle.However, the role of nitric oxide (NO) in glucose transport in thistissue remains unclear. To determine the role of NO in modulatingglucose transport, 2-deoxyglucose (2-DG) transport was measured in ratextensor digitorum longus (EDL) muscles that were exposed to either amaximally stimulating concentration of insulin or to an electricalstimulation protocol, in the presence ofN^G-monomethyl-L-arginine,a NOS inhibitor. In addition, EDL preparations were exposed to sodiumnitroprusside (SNP), an NO donor, in the presence of submaximal andmaximally stimulating concentrations of insulin. NOS inhibition reducedboth basal and exercise-enhanced 2-DG transport but had no effect oninsulin-stimulated 2-DG transport. Furthermore, SNP increased 2-DGtransport in a dose-responsive manner. The effects of SNP and insulinon 2-DG transport were additive when insulin was present inphysiological but not in pharmacological concentrations. Chronictreadmill training increased protein expression of both type I and typeIII NOS in soleus muscle homogenates. Our results suggest that NO maybe a potential mediator of exercise-induced glucose transport.

     

Phosphorylation of p70S6k correlates with increased skeletal muscle mass following resistance exercise

High-resistance exercise training results in an increase inmuscle wet mass and protein content. To begin to address the acute changes following a single bout of high-resistance exercise, a newmodel has been developed. Training rats twice a week for 6 wk resultedin 13.9 and 14.4% hypertrophy in the extensor digitorum longus (EDL)and tibialis anterior (TA) muscles, respectively. Polysome profilesafter high-resistance lengthening contractions suggest that the rate ofinitiation is increased. The activity of the 70-kDa S6 protein kinase(p70^S6k), a regulator oftranslation initiation, is also increased following high-resistancelengthening contractions (TA, 363 ± 29%; EDL, 353 ± 39%).Furthermore, the increase inp70^S6k activity 6 h after exercisecorrelates with the percent change in muscle mass after 6 wk oftraining (r = 0.998). The tightcorrelation between the activation ofp70^S6k and the long-term increasein muscle mass suggests thatp70^S6k phosphorylation may be agood marker for the phenotypic changes that characterize musclehypertrophy and may play a role in load-induced skeletal muscle growth.

     

Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa Zucker rats

The objective was to examine the effect of polyunsaturated fatty acid type (plant vs fish oil-derived n-3, compared to n-6 fatty acids in the presence of constant proportions of saturated, monounsaturated and polyunsaturated fatty acids) on obesity, insulin resistance and tissue fatty acid composition in genetically obese rats. Six-week-old fa/fa and lean Zucker rats were fed with a 10% (w/w) mixed fat diet containing predominantly flax-seed, menhaden or safflower oils for 9 weeks. There was no effect of dietary lipid on obesity, oral glucose tolerance (except t=60 min insulin), pancreatic function or molecular markers related to insulin, glucose and lipid metabolism, despite increased n-3 fatty acids in muscle and adipose tissue. The menhaden oil diet reduced fasting serum free fatty acids in both fa/fa and lean rats. These data suggest that n-3 composition does not alter obesity and insulin resistance in the fa/fa Zucker rat model when dietary lipid classes are balanced.     

Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers

Lynch, Gordon S., Alan Hayes, Siun P. Campbell, and David A. Williams. Effects of₂-agonist administration andexercise on contractile activation of skeletal muscle fibers.J. Appl. Physiol. 81(4):1610-1618, 1996.Clenbuterol, a₂-adrenoceptor agonist, hastherapeutic potential for the treatment of muscle-wasting diseases, yetits effects, especially at the single-fiber level, have not been fullycharacterized. Male C57BL/10 mice were allocated to three groups:Control-Treated mice were administered clenbuterol (2 mg ^· kg^{1 ·} day¹)via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) inaddition to receiving clenbuterol; and Control mice were sedentary anduntreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL)and soleus muscles. Fast fibers from the EDL and soleus muscles ofTreated mice exhibited decreases inCa²⁺ sensitivity. Enduranceexercise offset clenbuterol's effects, demonstrated by similarCa²⁺ sensitivities in theTrained-Treated and Control groups. Long-term clenbuterol treatment didnot affect the normalized maximal tension of fast or slow fibers butincreased the proportion of fast fibers in the soleus muscle. Trainingincreased the proportion of fibers with high and intermediate succinatedehydrogenase activity in the EDL and soleus muscles, respectively. Ifclenbuterol is to be used for treating muscle-wasting disorders, someform of low-intensity exercise might be encouraged such thatpotentially deleterious slow-to-fast fiber type transformations areminimized. Indeed, in the mouse, low-intensity exercise appears toprevent these effects.

     

Changes of Islet Size and Islet Size Distribution Resulting from Protein-Malnutrition in Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

TSE, ELIZABETH O, FRANCINE M GREGOIRE, BRIGITTE REUSENS, CLAUDE REMACLE, JOSEPH J HOET, PATRICIA R JOHNSON, JUDITH S STERN. Changes of islet size and islet size distribution resulting from protein malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats. Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Body-weight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (100 μm²) and a decrease in the population of large islets (>20,000 μ;m²). In lean and obese rats fed low protein, β-cell weight was significantly lower, B cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancreas in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.     

Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake

The hypothesisof this investigation was that insulin and muscle contraction, byincreasing the rate of skeletal muscle glucose transport, would biascontrol so that glucose delivery to the sarcolemma (and t tubule) andphosphorylation of glucose intracellularly would exert more influenceover glucose uptake. Because of the substantial increases in blood flow(and hence glucose delivery) that accompany exercise, we predicted thatglucose phosphorylation would become more rate determining duringexercise. The transsarcolemmal glucose gradient (TSGG; the glucoseconcentration difference across the membrane) is inversely related tothe degree to which glucose transport determines the rate of glucoseuptake. The TSGG was determined by using isotopic methods in consciousrats during euglycemic hyperinsulinemia [Ins; 20 mU/(kg · min); n = 7], during treadmill exercise (Ex,n = 6), and in sedentary,saline-infused rats (Bas, n = 13).Rats received primed, constant intravenous infusions of trace3-O-[³H]methyl-D-glucoseand [U-¹⁴C]mannitol.Then2-deoxy-[³H]glucosewas infused for the calculation of a glucose metabolic index(R_g). At the end of experiments,rats were anesthetized, and soleus muscles were excised. Total soleusglucose concentration and the steady-state ratio of intracellular toextracellular3-O-[³H]methyl-D-glucose(which distributes on the basis of the TSGG) were used to calculateranges of possible glucose concentrations ([G]) at theinner and outer sarcolemmal surfaces([G]_im and[G]_om, respectively).Soleus R_g was increased in Ins andfurther increased in Ex. In Ins, total soleus glucose,[G]_om, and the TSGGwere decreased compared with Bas, while[G]_im remained near 0. In Ex, total soleus glucose and[G]_im were increasedcompared with Bas, and there was not a decrease in[G]_om as was observedin Ins. In addition, accumulation of intracellular free2-deoxy-[³H]glucoseoccurred in soleus in both Ex and Ins. Taken together, these dataindicate that, in Ex, glucose phosphorylation becomes an importantlimitation to soleus glucose uptake. In Ins, both glucose delivery andglucose phosphorylation influence the rate of soleus glucose uptakemore than under basal conditions.

     

Protective role of extracellular chloride in fatigue of isolated mammalian skeletal muscle

A possible role of extracellular Cl^– concentration ([Cl^–]_o) in fatigue was investigated in isolated skeletal muscles of the mouse. When [Cl^–]_o was lowered from 128 to 10 mM, peak tetanic force was unchanged, fade was exacerbated (wire stimulation electrodes), and a hump appeared during tetanic relaxation in both nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Low [Cl^–]_o increased the rate of fatigue 1) with prolonged, continuous tetanic stimulation in soleus, 2) with repeated intermittent tetanic stimulation in soleus or EDL, and 3) to a greater extent with repeated tetanic stimulation when wire stimulation electrodes were used rather than plate stimulation electrodes in soleus. In nonfatigued soleus muscles, application of 9 mM K⁺ with low [Cl^–]_o caused more rapid and greater tetanic force depression, along with greater depolarization, than was evident at normal [Cl^–]_o. These effects of raised [K⁺]_o and low [Cl^–]_o were synergistic. From these data, we suggest that normal [Cl^–]_o provides protection against fatigue involving high-intensity contractions in both fast- and slow-twitch mammalian muscle. This phenomenon possibly involves attenuation of the depolarization caused by stimulation- or exercise-induced run-down of the transsarcolemmal K⁺ gradient. potassium; skeletal muscle contraction; membrane potential; myotonia     

Elevated growth hormone increases the Ca2+ sensitivity of slow- and fast-twitch skeletal muscle of female rats

To determine theeffect of plasma growth hormone (GH) on skeletal muscle function, wemeasured the free Ca²⁺concentration-tension relationship of slow-twitch (soleus) and fast-twitch (peroneus longus) muscles isolated from rats undergoing acromegaly in response to implanted, GH-secreting tumors. Muscles fromadult (9 mo) and aged rats (24 mo) were studied after the tumor-bearingrats weighed over 50% more than their age-matched controls.Ca²⁺-activated isometric tensionwas recorded from skinned muscle fibers. For soleus muscles, the freeCa²⁺ concentration producing 50%of maximal tension([Ca²⁺]₅₀)was 2.0 µM for rats with tumors and 3.4-3.6 µM for controls. For peroneus longus fibers,[Ca²⁺]₅₀shifted from 6.1-6.7 µM in controls to 3.5 µM after tumors were introduced into either adult or aged rats. Soleus muscle fibersfrom neonatal rats (14 days) were less sensitive toCa²⁺ than those isolated fromadult rats, having a[Ca²⁺]₅₀of 7.3 µM. The Ca²⁺ sensitivityof peroneus longus fibers did not change with age. We conclude thatsignificant increases in myofibrillarCa²⁺ sensitivity occur in skeletalmuscles undergoing rapid growth induced by GH-secreting tumors.