Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days

 The effects of two different duration spaceflights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight. Accepted: 8 January 1998     

Fiber type composition of four hindlimb muscles of adult Fisher 344 rats

 The limb and trunk muscles of adult rats express four myosin heavy chain (MHC) isoforms, one slow (MHCI) and three fast (MHCIIa, MHCIId, and MHCIIb). The distribution of these isoforms correlates with fiber types delineated using myofibrillar actomyosin adenosine triphosphatase (mATPase) histochemistry. For example, type I fibers express MHCI and fiber types IIA, IID, and IIB express MHCIIa, MHCIId, and MHCIIb, respectively. Fibers containing only one MHC isoform have been termed ”pure” fibers. Recent evidence suggests that a population of ”hybrid” fibers exist in rat skeletal muscle which contain two MHC isoforms. The purpose of the present investigation was to document the entire range of histochemically defined ”pure” and ”hybrid” fiber types in untreated muscles of the young adult Fisher 344 rat hindlimb. The selected hindlimb muscles (soleus, tibialis anterior, extensor digitorum longus, and gastrocnemius muscles) were removed from 12 male rats and analyzed for muscle fiber type distribution, cross-sectional area, and MHC content. Care was taken to delineate eight fiber types (I, IC, IIC, IIA, IIAD, IID, IIDB, and IIB) using refined histochemical techniques. Hybrid fibers were found to make up a considerable portion of the muscles examined (a range of 8.8–17.8% of the total). The deep red portion of the gastrocnemius muscle contained the largest number of hybrid fibers, most of which were the fast types IIAD (8.5±2.8%) and IIDB (5.2±2.3%). In conclusion, hybrid fibers make up a considerable portion of normal rat limb musculature and are an important population that should not be ignored. Accepted: 15 October 1998     

Correlation between myofibrillar ATPase activity and myosin heavy chain composition in single human muscle fibers.

Single human muscle fibers were analysed using a combination of histochemical and biochemical techniques. Routine myofibrillar adenosine triphosphatase (mATPase) histochemistry revealed a continuum of staining intensities between the fast fiber types IIA and IIB (type IIAB fibers) after preincubation at pH 4.6. Electrophoretic analysis of single, histochemically-identified fibers demonstrated a correlation between the staining intensity and the myosin heavy chain (MHC) composition. All fibers classified as type I contained exclusively MHCI and all type IIA fibers contained only MHCIIa. Type IIAB fibers displayed variable amounts of both MHCIIa and MHCIIb; the greater the staining intensity of these fibers after preincubation at pH 4.6, the greater the percentage of MHCIIb. Those fibers histochemically classified as type IIB contained either entirely MHCIIb or, in addition to MHCIIb, a small amount of MHCIIa. These data establish a correlation between the mATPase activity and MHC content in single human muscle fibers.     

Correlation between myofibrillar ATPase activity and myosin heavy chain composition in single human muscle fibers

Summary Single human muscle fibers were analysed using a combination of histochemical and biochemical techniques. Routine myofibrillar adenosine triphosphatase (mATPase) histochemistry revealed a continuum of staining intensities between the fast fiber types IIA and IIB (type IIAB fibers) after preincubation at pH 4.6. Electrophoretic analysis of single, histochemically-identified fibers demonstrated a correlation between the staining intensity and the myosin heavy chain (MHC) composition. All fibers classified as type I contained exclusively MHCI and all type IIA fibers contained only MHCIIa. Type IIAB fibers displayed variable amounts of both MHCIIa and MHCIIb; the greater the staining intensity of these fibers after preincubation at pH 4.6, the greater the percentage of MHCIIb. Those fibers histochemically classified as type IIB contained either entirely MHCIIb or, in addition to MHCIIb, a small amount of MHCIIa. These data establish a correlation between the mATPase activity and MHC content in single human muscle fibers.     

Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space.

The decline in muscle function is associated with an age-related decrease in muscle mass and an age-related decline in strength. However, decreased strength is not solely due to decreased muscle mass. The age-related decline in muscle-specific force (force/muscle cross-sectional area), a measure of intrinsic muscle function, also contributes to age-related strength decline, and the mechanisms by which this occurs are only partially known. Moreover, changes in the extracellular space could have a profound effect on skeletal muscle function. Life-long calorie restriction in rodents has shown to be a powerful anti-aging intervention. In this study, we examine whether calorie restriction is able to attenuate the loss of muscle function and elevations in extracellular space associated with aging. We hypothesize that calorie restriction attenuates the age-associated decline in specific force and increases in extracellular space. Measurements of in vitro contractile properties of the extensor digitorum longus (type II) and soleus (type I) muscles from 12-mo and 26- to 28-mo-old ad libitum-fed, as well as 27- to 28-mo-old life-long calorie-restricted male Fischer 344 rats, were performed. We found that calorie restriction attenuated the age-associated decline in muscle mass-to-body mass ratio (mg/g) and strength-to-body mass ratio (N/kg) in the extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle (P > 0.05). Importantly, muscle-specific force (N/cm2) in the extensor digitorum longus, but not in the soleus muscle, of the old calorie-restricted rats was equal to that of the young 12-mo-old animals. Moreover, the age-associated increase in extracellular space was reduced in the fast-twitch extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle with calorie restriction. We also found a significant correlation between the extracellular space and the muscle-specific force in the extensor digitorum longus (r = -0.58; P < 0.05) but not in the soleus muscle (r = -0.38; P > 0.05). Hence, this study shows a loss of muscle function with age and suggests that long-term calorie restriction is an effective intervention against the loss of muscle function with age.     

Age effect on expression of myosin heavy and light chain isoforms in suspended rat soleus muscle.

This study was designed to test the hypothesis that myosin heavy (MHC) and light chain (MLC) plasticity resulting from hindlimb suspension (HS) is an age-dependent process. By using an electrophoretic technique, the distribution of MHC and MLC isoforms was quantitatively evaluated in the soleus muscles from 3- or 12-wk-old rats after 1-3 wk of HS treatment was maintained. In normal 12- and 15-wk-old rats, the soleus muscles contained a predominance of MHCI ( approximately 94%) with small amounts of MHCIIa, but not MHCIId or MHCIIb. The suspended muscles of adult rats were characterized by the appearance of MHCIIb and MHCIId, the latter reaching approximately 6% after 3 wk of HS treatment. In contrast to changes in MHC, HS did not induce a transition in the MLC pattern in the soleus muscles from adult rats. Compared with adult rats, in juveniles HS had a much more pronounced effect on the shift toward faster MHC and MLC isoform expression. The soleus muscles of 6-wk-old rats after 3 wk of HS were composed of 37.0% MHCI, 19.1% MHCIIa, 23.7% MHCIId, and 20.2% MHCIIb. Changes in MLC isoforms consisted of an increase in MLC1f and MLC2f concomitant with a decrease in MLC2s. These results indicate the existence of a differential effect of HS on MHC and MLC transitions that appears to be age dependent. They also suggest that the suspended soleus muscles from young rats may acquire the intrinsic contractile properties that are intermediate between those in the normal soleus and typical fast-twitch skeletal muscles.     

Blood flow and glycogen use in hypertrophied rat muscles during exercise

Previous findings suggest that skeletal muscle that has enlarged as a result of removal of synergistic muscles has a similar metabolic capacity and improved resistance to fatigue compared with normal muscle. The purpose of the present study was to follow blood flow and glycogen loss patterns in hypertrophied rat plantaris plantaris and soleus muscles during treadmill exercise to provide information on the adequacy of perfusion of the muscles during in vivo exercise. Thirty days following surgical removal of gastrocnemius muscle, blood flows (determined with radiolabeled microspheres) and glycogen concentrations were determined in all of the ankle extensor muscles of experimental and sham-operated control rats during preexercise and after 5-6 min of treadmill exercise at 15 m/min. There were no differences (P greater than 0.05) in blood flows per unit mass or glycogen concentrations between control and hypertrophied plantaris or soleus muscles at either time, although both muscles were larger (P less than 0.05) in the experimental group (plantaris: 95%; soleus: 40%). None of the other secondary ankle extensor muscles (tibialis posterior, flexor digitorum longus or flexor hallicus longus) hypertrophied in response to removal of gastrocnemius. These results provide indirect evidence that O2 delivery in the enlarged muscles is not compromised during low-intensity treadmill exercise due to limited perfusion.     

Insulin binding and 2-deoxy-D-glucose uptake in fast- and slow-twitch mouse skeletal muscle at 18 and 37 degrees C

Insulin binding, insulin degradation, and 2-deoxyglucose uptake were examined at 18 and 37 degrees C in soleus and extensor digitorum longus muscles of mice. Insulin binding and degradation were greater in the soleus than in the extensor digitorum longus at both temperatures (p less than 0.05). At 37 degrees C, binding was decreased in both muscles while percentage degradation was increased in comparison with 18 degrees C (p less than 0.05). Dose--response curves (percentage of binding at 4 nM of insulin) remained the same for both muscles at the two temperatures. Basal (no insulin) 2-deoxyglucose uptake was increased at 37 degrees C in the extensor digitorum longus but not the soleus. Insulin responsiveness in terms of the amount of 2-deoxyglucose taken up per femtomole of insulin bound was almost identical for the two muscles at 18 degrees C, whereas at 37 degrees C it was increased more in the soleus than in the extensor digitorum longus. The results indicate that in the presence of physiological concentrations of insulin (0.2-4 nM), insulin binding trends are minimally affected by increased temperature. In contrast, the ability of insulin to stimulate 2-deoxyglucose uptake varies between the two temperatures, and at the higher temperature between fast- and slow-twitch muscle.     

Effects of unweighting and clenbuterol on myosin light and heavy chains in fast and slow muscles of rat

To investigate the plasticityof slow and fast muscles undergoing slow-to-fast transition, rat soleus(SOL), gastrocnemius (GAS), and extensor digitorum longus (EDL) muscleswere exposed for 14 days to 1) unweighting by hindlimbsuspension (HU), or 2) treatment with the₂-adrenergic agonist clenbuterol (CB), or 3)a combination of both (HU-CB). In general, HU elicited atrophy, CBinduced hypertrophy, and HU-CB partially counteracted the HU-induced atrophy. Analyses of myosin heavy (MHC) and light chain (MLC) isoformsrevealed HU- and CB-induced slow-to-fast transitions in SOL (increasesof MHCIIa with small amounts of MHCIId and MHCIIb) and theupregulation of the slow MHCIa isoform. The HU- and CB-induced changesin GAS consisted of increases in MHCIId and MHCIIb("fast-to-faster transitions"). Changes in the MLC composition ofSOL and GAS consisted of slow-to-fast transitions and mainlyencompassed an exchange of MLC1s with MLC1f. In addition, MLC3f waselevated whenever MHCIId and MHCIIb isoforms were increased. Becausethe EDL is predominantly composed of type IID and IIB fibers, HU, CB,and HU-CB had no significant effect on the MHC and MLC patterns.

     

Effect of high-intensity exercise training on functional capacity of limb skeletal muscle

The purpose of this study was to determine whether a program of regular sprint exercise training alters the functional properties or protects against the development of fatigue in fast- and slow-twitch rat skeletal muscle. The training program consisted of 6 sprints of 4.5-min duration at 40 m/min and 15% slope with 2.5-min rest intervals, performed 5 days/wk for 6 wk. The exercise program significantly increased (P less than 0.05) citrate synthase activity (mumol X g-1 X min-1) in the predominantly type I soleus (SOL) from 28 +/- 2 to 44 +/- 2; the type IIb superficial region of the vastus lateralis (SVL) from 10 +/- 1 to 16 +/- 1; and the type IIa deep region of the vastus lateralis (DVL) from 34 +/- 2 to 53 +/- 2. Phosphofructokinase activity (mumol X g-1 X min-1) also increased with training in the SOL (17 +/- 1 vs. 23 +/- 1) and the DVL (64 +/- 5 vs. 79 +/- 5). Sprint training reduced (P less than 0.05) the contraction time (CT) (111 +/- 7 vs. 92 +/- 3 ms) and the one-half relaxation time (118 +/- 3 vs. 104 +/- 2 ms) in the slow-twitch soleus. The exercise program also induced a decreased CT in the fast-twitch extensor digitorum longus (EDL), but significance was limited to the P less than 0.1 level. Muscle fatigue was produced by electrical stimulation at 45 trains/min and either 15 trains/min in SOL or 10 trains/min in the EDL and SVL for 1, 5, or 10 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of endurance exercise-training on single-fiber contractile properties of insulin-treated streptozotocin-induced diabetic rats.

The purpose of this study was to characterize the contractile properties of individual skinned muscle fibers from insulin-treated streptozotocin-induced diabetic rats after an endurance exercise training program. We hypothesized that single-fiber contractile function would decrease in the diabetic sedentary rats and that endurance exercise would preserve the function. In the study, 28 rats were assigned to either a nondiabetic sedentary, a nondiabetic exercise, a diabetic sedentary, or a diabetic exercise group. Rats in the diabetic groups received subcutaneous intermediate-lasting insulin daily. The exercise-trained rats ran on a treadmill at a moderate intensity for 60 min, five times per week. After 12 wk, the extensor digitorum longus and soleus muscles were dissected. Single-fiber diameter, Ca(2+)-activated peak force, specific tension, activation threshold, and pCa(50) as well as the myosin heavy chain isoform expression (MHC) were determined. We found that in MHC type II fibers from extensor digitorum longus muscle, diameters were significantly smaller from diabetic sedentary rats compared with nondiabetic sedentary rats (P < 0.001). Among the nondiabetic rats, fiber diameters were smaller with exercise (P = 0.038). The absolute force-generating capacity of single fibers was lower in muscles from diabetic rats. There was greater specific tension (force normalized to cross-sectional area) by fibers from the rats that followed an endurance exercise program compared with sedentary. From the results, we conclude that alterations in the properties of contractile proteins are not implicated in the decrease in strength associated with diabetes and that endurance-exercise training does not prevent or increase muscle weakness in diabetic rats.     

Increased submaximal insulin-stimulated glucose uptake in mouse skeletal muscle after treadmill exercise.

The primary purpose of this study was to determine the effect of prior exercise on insulin-stimulated glucose uptake with physiological insulin in isolated muscles of mice. Male C57BL/6 mice completed a 60-min treadmill exercise protocol or were sedentary. Paired epitrochlearis, soleus, and extensor digitorum longus (EDL) muscles were incubated with [3H]-2-deoxyglucose without or with insulin (60 microU/ml) to measure glucose uptake. Insulin-stimulated glucose uptake for paired muscles was calculated by subtracting glucose uptake without insulin from glucose uptake with insulin. Muscles from other mice were assessed for glycogen and AMPK Thr172 phosphorylation. Exercised vs. sedentary mice had decreased glycogen in epitrochlearis (48%, P < 0.001), soleus (51%, P < 0.001), and EDL (41%, P < 0.01) and increased AMPK Thr172 phosphorylation (P < 0.05) in epitrochlearis (1.7-fold), soleus (2.0-fold), and EDL (1.4-fold). Insulin-independent glucose uptake was increased 30 min postexercise vs. sedentary in the epitrochlearis (1.2-fold, P < 0.001), soleus (1.4-fold, P < 0.05), and EDL (1.3-fold, P < 0.01). Insulin-stimulated glucose uptake was increased (P < 0.05) approximately 85 min after exercise in the epitrochlearis (sedentary: 0.266 +/- 0.045 micromol x g(-1) x 15 min(-1); exercised: 0.414 +/- 0.051) and soleus (sedentary: 0.102 +/- 0.049; exercised: 0.347 +/- 0.098) but not in the EDL. Akt Ser473 and Akt Thr308 phosphorylation for insulin-stimulated muscles did not differ in exercised vs. sedentary. These results demonstrate enhanced submaximal insulin-stimulated glucose uptake in the epitrochlearis and soleus of mice 85 min postexercise and suggest that it will be feasible to probe the mechanism of enhanced postexercise insulin sensitivity by using genetically modified mice.     

Protein kinase Cα activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

Exercise-induced phosphorylation of FXYD1 is a potential important regulator of Na(+)-K(+)-pump activity. It was investigated whether skeletal muscle contractions induce phosphorylation of FXYD1 and whether protein kinase Cα (PKCα) activity is a prerequisite for this possible mechanism. In part 1, human muscle biopsies were obtained at rest, after 30 s of high-intensity exercise (166 ± 31% of Vo(2max)) and after a subsequent 20 min of moderate-intensity exercise (79 ± 8% of Vo(2max)). In general, FXYD1 phosphorylation was increased compared with rest both after 30 s (P < 0.05) and 20 min (P < 0.001), and more so after 20 min compared with 30 s (P < 0.05). Specifically, FXYD1 ser63, ser68, and combined ser68 and thr69 phosphorylation were 26-45% higher (P < 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation was investigated in electrically stimulated soleus and EDL muscles from PKCα knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68 phosphorylation to be increased (P < 0.001) in WT soleus muscles but to be reduced (P < 0.001) in WT extensor digitorum longus. In contrast, contractile activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68 phosphorylation are fiber-type specific and dependent on PKCα activity.     

Potentiation of the halothane-cooling contractures of mammalian muscles by denervation

Denervation potentiated the cooling-induced contractures and the halothane-cooling contractures of isolated extensor digitorum longus and soleus muscles of the mouse. These effects were more striking in extensor digitorum longus than in soleus muscles. Significant increases in the peak amplitudes of the halothane-cooling contractures of both muscles and of the cooling contractures of soleus muscle were observed within 2 and 7 days of denervation. The potentiation of the contractures persisted for 90 days, the period of this study. Denervation (greater than 2 days) endowed extensor digitorum longus with the ability to generate cooling contractures in the absence of halothane. The rate of tension development of cooling-induced contractures in the absence or presence of halothane was significantly greater in denervated (2-90 days) than in innervated muscles. Denervation also reduced the effectiveness of procaine in inhibiting the halothane-cooling contractures. It is proposed that the potentiation of cooling-induced contractures in denervated muscles results primarily from an increase in the rate of efflux and in the quantity of Ca2+ released from the sarcoplasmic reticulum, upon cooling and (or) when challenged with halothane.     

Histochemical fiber type distribution and epinephrine sensitivity in normal and cross-transplanted rat muscles

The metabolic integrity of fully regenerated transplants was investigated by measuring induced changes in glycogen concentration. The extensor digitorum longus and the soleus muscles were cross transplanted: the extensor digitorum longus into the soleus muscle bed (SOLT) and the soleus muscle into the extensor digitorum longus bed (EDLT). The histochemical fiber type distribution of the regenerated muscles was determined and was found to transform in cross-transplanted EDLT and SOLT. After transplantation and regeneration, both muscles had initially low glycogen concentrations. However, the EDLT glycogen concentration was not significantly different from that of the contralateral extensor digitorum longus control muscle after 60 days. In the SOLT, glycogen gradually increased but remained less than in the contralateral soleus control muscle. SOLT and control soleus muscles responded with a significant glycogen depletion to an epinephrine dose two orders of magnitude less than the lowest dose affecting glycogen levels in EDLT and extensor digitorum longus muscles. These results indicate that transplanted muscles are capable of regenerating normal glycogenolytic responses and that the sensitivity of the response observed depends on the site of transplantation and is related to the type of innervation and histochemical fiber type.     

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.     

Effects of exercise on insulin binding and glucose metabolism in muscle

To elucidate the mechanism of enhanced insulin sensitivity by muscle after exercise, we studied insulin binding, 2-deoxy-D-[1-14C]glucose (2-DOG) uptake and [5-3H]glucose utilization in glycolysis and glycogenesis in soleus and extensor digitorum longus (EDL) muscles of mice after 60 min of treadmill exercise. In the soleus, glycogenesis was increased after exercise (P less than 0.05) and remained sensitive to the action of insulin. Postexercise insulin-stimulated glycolysis was also increased in the soleus (P less than 0.05). In the EDL, glycogenesis was increased after exercise (P less than 0.05). However, this was already maximal in the absence of insulin and was not further stimulated by insulin (0.1-4 nM). The disposal of glucose occurred primarily via the glycolytic pathway (greater than 60%) in the soleus and EDL at rest and after exercise. The uptake of 2-DOG uptake was not altered in the soleus after exercise (4 h incubation at 18 degrees C). However, with 1-h incubations at 37 degrees C, a marked increase in 2-DOG uptake after exercise was observed in the soleus (P less than 0.05) in the absence (0 nM) and presence of insulin (0.2-4 nM) (P less than 0.05). A similar postexercise increase in 2-DOG uptake occurred in EDL. Despite the marked increase in glucose uptake and metabolism, no changes in insulin binding were apparent in either EDL or soleus at 37 degrees C or 18 degrees C. This study shows that the postexercise increase of glucose disposal does not appear to be directly attributable to increments in insulin binding to slow-twitch and fast-twitch muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle

We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding l-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles.     

Exercise training reduces skeletal muscle membrane arachidonate in the obese (fa/fa) Zucker rat

Compared with the lean(Fa/) genotype, obese(fa/fa) Zucker rats have arelative deficiency of muscle phospholipid arachidonate, and skeletalmuscle arachidonate in humans is positively correlated with insulinsensitivity. To assess the hypothesis that the positive effects ofexercise training on insulin sensitivity are mediated by increasedmuscle arachidonate, we randomized 20 lean and 20 obese weanling maleZucker rats to sedentary or treadmill exercise groups. After 9 wk,fasting serum, three skeletal muscles (white gastrocnemius, soleus, andextensor digitorum longus), and heart were obtained. Fasting insulinwas halved by exercise training in the obese rat. In whitegastrocnemius and extensor digitorum longus (fast-twitch muscles), butnot in soleus (a slow-twitch muscle) or heart, phospholipidarachidonate was lower in obese than in lean rats(P < 0.001). In all muscles,exercise in the obese rats reduced arachidonate(P < 0.03, by ANOVA contrast). Weconclude that improved insulin sensitivity with exercise in the obesegenotype is not mediated by increased muscle arachidonate and thatreduced muscle arachidonate in obese Zucker rats is unique tofast-twitch muscles.