Functional deficits in medial gastrocnemius grafts in rats: relation to muscle metabolism and beta -AR regulation

Larkin, Lisa M., John A. Faulkner, Richard T. Hinkle, CherylA. Hassett, Mark A. Supiano, and Jeffrey B. Halter.Functional deficits in medial gastrocnemius grafts in rats:relation to muscle metabolism and -AR regulation.J. Appl. Physiol. 83(1): 67-73, 1997.This study tested the hypothesis that alterations in the metabolic integrity of grafted muscle contribute to its diminished ability to sustain power. Compared with control muscles, muscles studied 120 days after the grafting procedure had lower specific forceand sustained power. The sustained power protocol resulted in adepletion of muscle glycogen in control (83%) and grafted (85%)animals. Grafts had lower pre- and poststimulation glycogen, diminishedcitrate synthase activity, and greater hexokinase activity. Nodifferences were observed in phosphofructokinase activity, glucosetransporter GLUT-4 content, fiber type, -adrenergic-receptor (-AR) density, or binding affinity. Isoproterenol-stimulated adenylyl cyclase activity was lower in grafted vs. control muscle, suggesting an uncoupling of the -AR-effector complex. Thus the diminished ability of the grafted muscle to sustain power may beexplained, in part, by a decrease in energy available from glycogenstores and/or a decrease in oxidative capacity.

     

Muscle adaptations to hindlimb suspension in mature and old Fischer 344rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and oldFischer 344 rats. J. Appl. Physiol.82(6): 1875-1881, 1997.We examined skeletal and cardiac muscleresponses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS)activities and GLUT-4 glucose transporter protein level, which arecoregulated in many instances of altered neuromuscular activity, wereanalyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA),extensor digitorum longus (EDL), and left ventricle. Protein contentwas significantly (P < 0.05) lowerin all four hindlimb muscles after suspension compared with controls inboth mature (21-44%) and old (17-43%) rats. Old ratsexhibited significantly lower CS activities than mature rats for theSol, Pl, and TA. HK activities were significantly lower in the old ratsfor the Pl (19%) and TA (33%), and GLUT-4 levels were lower in theold rats for the TA (38%) and EDL (24%) compared with the maturerats. Old age was also associated with a decrease in CS activity (12%)and an increase in HK activity (14%) in cardiac muscle. CS activitieswere lower in the Sol (20%) and EDL (18%) muscles from maturesuspended rats and in the Sol (25%), Pl (27%), and EDL (25%) musclesfrom old suspended rats compared with corresponding controls. However,suspension was associated with significantly higher HK activities forall four hindlimb muscles examined, in both old (16-57%) andmature (10-43%) rats, and higher GLUT-4 concentrations in the TAmuscles of the old rats (68%) but not the mature rats. These resultsindicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, andthese variables are not coregulated during suspension. Finally, old ratskeletal muscle appears to respond to suspension to a similar orgreater degree than mature rat muscle responds.

     

Reduced lipoprotein lipase activity in postural skeletal muscle during aging.

Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein metabolism in muscle. However, the effect of aging on LPL regulation in skeletal muscle is unknown. We report the effect of aging on LPL regulation in the soleus (red oxidative postural) muscle and the tibialis anterior (white glycolytic non-weight-bearing) muscle in 4- and 24-mo-old Fischer 344 rats and 18- and 31-mo-old Fischer 344 x Brown-Norway F1 (F-344 x BN F1) rats. Total and heparin-releasable LPL (HR-LPL) activities were decreased 38% (P < 0.01) and 52% (P < 0.05), respectively, in the soleus muscle of the older Fischer 344 rats. There was a 32% reduction (P < 0.05) of total LPL protein mass in the soleus muscle with aging. The results were confirmed in another strain. A decrease of total LPL activity (-50%, P < 0.05) was also found in the soleus muscle between 18- and 31-mo-old F-344 x BN F1 rats. LPL mRNA concentration in the soleus muscle was not different between ages. Total LPL protein mass was reduced by 46% (P < 0.05) in the soleus muscle of the 31-mo-old F-344 x BN F1 rats. In the tibialis anterior muscle, neither LPL activity nor mRNA concentration was affected by age in either strain. In conclusion, LPL regulation in a non-weight-bearing muscle was not affected by aging. However, there was a pronounced reduction in LPL activity and LPL protein mass in postural muscle with aging.     

Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training

Kawanaka, Kentaro, Izumi Tabata, Shigeru Katsuta, andMitsuru Higuchi. Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training.J. Appl. Physiol. 83(6):2043-2047, 1997.After running training, which increased GLUT-4protein content in rat skeletal muscle by <40% compared with controlrats, the training effect on insulin-stimulated maximal glucosetransport (insulin responsiveness) in skeletal muscle was short lived(24 h). A recent study reported that GLUT-4 protein content in ratepitrochlearis muscle increased dramatically (~2-fold) after swimmingtraining (J.-M. Ren, C. F. Semenkovich, E. A. Gulve, J. Gao, andJ. O. Holloszy. J. Biol.Chem. 269, 14396-14401, 1994).Because GLUT-4 protein content is known to be closely related toskeletal muscle insulin responsiveness, we thought it possible that thetraining effect on insulin responsiveness may remain for >24 h afterswimming training if GLUT-4 protein content decreases gradually fromthe relatively high level and still remains higher than control levelfor >24 h after swimming training. Therefore, we examined thispossibility. Male Sprague-Dawley rats swam 2 h a day for 5 days with aweight equal to 2% of body mass. Approximately 18, 42, and 90 h aftercessation of training, GLUT-4 protein concentration and2-[1,2-³H]deoxy-D-glucosetransport in the presence of a maximally stimulating concentration ofinsulin (2 mU/ml) were examined by using incubated epitrochlearismuscle preparation. Swimming training increased GLUT-4 proteinconcentration and insulin responsiveness by 87 and 85%, respectively,relative to age-matched controls when examined 18 h after training.Forty-two hours after training, GLUT-4 protein concentration andinsulin responsiveness were still higher by 52 and 51%, respectively,in muscle from trained rats compared with control. GLUT-4 proteinconcentration and insulin responsiveness in trained muscle returned tosedentary control level within 90 h after training. We conclude that1) the change in insulinresponsiveness during detraining is directly related to muscle GLUT-4protein content, and 2)consequently, the greater the increase in GLUT-4 protein content thatis induced by training, the longer an effect on insulin responsivenesspersists after the training.

     

Decreased insulin action on muscle glucose transport after eccentric contractions in rats

Asp, Sven, and Erik A. Richter. Decreased insulinaction on muscle glucose transport after eccentric contractions in rats. J. Appl. Physiol. 81(5):1924-1928, 1996.We have recently shown that eccentriccontractions (Ecc) of rat calf muscles cause muscle damage anddecreased glycogen and glucose transporter GLUT-4 protein content inthe white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl.Physiol. 79: 1338-1345, 1995). To study whetherthese changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 µU/ml) 2 daysafter one-legged eccentric contractions of the calf muscles. Comparedwith control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG,whereas it was lower (P < 0.05) atboth submaximal and maximal insulin concentrations in the Ecc-WG and atmaximal concentrations in the Ecc-RG. In the Ecc-S, the glucosetransport was unchanged in hindquarters perfused in the absence orpresence of a submaximal stimulating concentration of insulin, whereasit was slightly (P < 0.05) higherduring maximal insulin stimulation compared with control S. At the endof perfusion the glycogen concentrations were lower in bothEcc-gastrocnemius muscles compared with control muscles at all insulinconcentrations. Fractional velocity of glycogen synthase increasedsimilarly with increasing insulin concentrations in Ecc- and control WGand RG. We conclude that insulin action on glucose transport but notglycogen synthase activity is impaired in perfused muscle exposed toprior eccentric contractions.

     

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

Marsh, Daniel R., David S. Criswell, James A. Carson, andFrank W. Booth. Myogenic regulatory factors during regeneration ofskeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270-1275, 1997.Myogenicfactor mRNA expression was examined during muscle regeneration afterbupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of thetibialis anterior muscle in the young rats had recovered to controlvalues by 21 days postbupivacaine injection but in adult and old ratsremained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA wassignificantly increased in muscles of young, adult, and old rats 5 daysafter bupivacaine injection. Subsequently, myogenin mRNA levels inyoung rat muscle decreased to postinjection control values byday 21 but did not return to controlvalues in 28-day regenerating muscles of adult and old rats. Theexpression of MyoD mRNA was also increased in muscles atday 5 of regeneration in young, adult,and old rats, decreased to control levels by day14 in young and adult rats, and remained elevated inthe old rats for 28 days. In summary, either a diminished ability todownregulate myogenin and MyoD mRNAs in regenerating muscle occurs inold rat muscles, or the continuing myogenic effort includes elevatedexpression of these mRNAs.

     

More tetanic contractions are required for activating glucose transport maximally in trained muscle

Kawanaka, Kentaro, Izumi Tabata, and MitsuruHiguchi. More tetanic contractions are requiredfor activating glucose transport maximally in trained muscle.J. Appl. Physiol. 83(2): 429-433, 1997.Exercise training increases contraction-stimulated maximalglucose transport and muscle glycogen level in skeletal muscle.However, there is a possibility that more muscle contractions arerequired to maximally activate glucose transport in trained than inuntrained muscle, because increased glycogen level after training mayinhibit glucose transport. Therefore, the purpose of this study was toinvestigate the relationship between the increase in glucose transportand the number of tetanic contractions in trained and untrained muscle.Male rats swam 2 h/day for 15 days. In untrained epitrochlearis muscle,resting glycogen was 26.6 µmol glucose/g muscle. Ten, 10-s-longtetani at a rate of 1 contraction/min decreased glycogen level to 15.4 µmol glucose/g muscle and maximally increased2-deoxy-D-glucose(2-DG) transport. Training increasedcontraction-stimulated maximal 2-DG transport (+71%;P < 0.01), GLUT-4 protein content(+78%; P < 0.01), and restingglycogen level (to 39.3 µmol glucose/g muscle;P < 0.01) on the next day after thetraining ended, although this training effect might be due, at least inpart, to last bout of exercise. In trained muscle, 20 tetani werenecessary to maximally activate glucose transport. Twenty tetanidecreased muscle glycogen to a lower level than 10 tetani (18.9 vs.24.0 µmol glucose/g muscle; P < 0.01). Contraction-stimulated 2-DG transport was negatively correlatedwith postcontraction muscle glycogen level in trained (r = 0.60;P < 0.01) and untrained muscle(r = 0.57;P < 0.01).

     

Voluntary exercise training enhances glucose transport in muscle stimulated by insulin-like growth factor I

Hokama, Jason Y., Ryan S. Streeper, and Erik J. Henriksen.Voluntary exercise training enhances glucose transport in muscle stimulated by insulin-like growth factor I. J. Appl. Physiol. 82(2): 508-512, 1997.Skeletal muscle glucosetransport can be regulated by hormonal factors such as insulin andinsulin-like growth factor I (IGF-I). Although it is well establishedthat exercise training increases insulin action on muscle glucosetransport, it is currently unknown whether exercise training leads toan enhancement of IGF-I-stimulated glucose transport in skeletal muscle. Therefore, we measured glucose transport activity [by using 2-deoxy-D-glucose (2-DG)uptake] in the isolated rat epitrochlearis muscle stimulated bysubmaximally and maximally effective concentrations of insulin (0.2 and13.3 nM) or IGF-I (5 and 50 nM) after 1, 2, and 3 wk of voluntary wheelrunning (WR). After 1 wk of WR, both submaximal andmaximal insulin-stimulated 2-DG uptake rates were significantly(P < 0.05) enhanced (43 and 31%)compared with those of sedentary controls, and these variables werefurther increased after 2 (86 and 57%) and 3 wk (71 and 70%) ofWR. Submaximal and maximal IGF-I-stimulated 2-DG uptakerates were significantly enhanced after 1 wk of WR (82 and 61%), andthese increases did not expand substantially after 2 (71 and 58%) and3 wk (96 and 70%) of WR. This enhancement of hormone-stimulated 2-DGuptake in WR muscles preceded any alteration in glucose transporter(GLUT-4) protein level, which increased only after 2 (24%) and 3 wk(54%) of WR. Increases in GLUT-4 protein were significantly correlated (r = 0.844) with increases in citratesynthase. These results indicate that exercise training can enhanceboth insulin-stimulated and IGF-I-stimulated muscle glucose transportactivity and that these improvements can develop without an increase inGLUT-4 protein.

     

Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart

Osborn, Brett A., June T. Daar, Richard A. Laddaga, Fred D. Romano, and Dennis J. Paulson. Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J. Appl. Physiol. 82(3): 828-834, 1997.This study determined whether dynamic exercise training ofdiabetic rats would increase the expression of the GLUT-4 glucosetransport protein in prepared cardiac sarcolemmal membranes. Fourgroups were compared: sedentary control, sedentary diabetic, trainedcontrol, and trained diabetic. Diabetes was induced by intravenousstreptozotocin (60 mg/kg). Trained control and diabetic rats were runon a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk.Sarcolemmal membranes were isolated by using differentialcentrifugation, and the activity of sarcolemmalK⁺-p-nitrophenylphosphatase( pNPPase; an indicator ofNa⁺-K⁺-adenosinetriphosphataseactivity) was quantified. Hearts from the sedentary diabetic groupexhibited a significant depression of sarcolemmal pNPPaseactivity. Exercise training did not significantly alterpNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative tocontrol rats. In the trained diabetic animals, sarcolemmal GLUT-4protein levels were only reduced by 50% relative to control values,whereas GLUT-4 mRNA were returned to control levels. The increase inmyocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heartby enhancing myocardial glucose oxidation and cardiac performance

     

Synergist muscle ablation and recovery from nerve-repair grafting: contractile and metabolic function.

After nerve-repair grafting of medial gastrocnemius muscle, there is incomplete recovery of specific force and sustainable power, perhaps due to overcompensation by synergistic muscles. We hypothesized that increased workload due to synergist ablation would enhance graft recovery. Contractile and metabolic properties of control and nerve-repair grafted muscles, with and without synergist ablation, were determined after 120 days recovery. Specific force (N/cm(2)) and normalized power (W/kg) were less in the experimental groups compared with controls. Sustained power (W/kg) in the synergist-ablated nerve-repair grafted muscle was higher than nerve-repair grafted muscle, returning to control values. GLUT-4 protein was higher and glycogen content was diminished in both synergist-ablated groups. In summary, synergist ablation did not enhance the recovery of specific force or normalized power, but sustained power did recover, suggesting that metabolic and not mechanical parameters were responsible for this recovery. The enhanced endurance after synergist ablation was accompanied by increased GLUT-4 protein, suggesting a role for increased uptake of circulating glucose during contraction.     

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.

     

Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content

Asp, Sven, Thomas Rohde, and Erik A. Richter. Impairedmuscle glycogen resynthesis after a marathon is not caused by decreasedmuscle GLUT-4 content. J. Appl.Physiol. 83(5): 1482-1485, 1997.Our purpose wasto investigate whether the slow rate of muscle glycogen resynthesisafter a competitive marathon is associated with a decrease in the totalmuscle content of the muscle glucose transporter (GLUT-4). Sevenwell-trained marathon runners participated in the study, and musclebiopsies were obtained from the lateral head of the gastrocnemiusmuscle before, immediately after, and 1, 2, and 7 days after themarathon, as were venous blood samples. Muscle GLUT-4 content wasunaltered over the experimental period. Muscle glycogen concentrationwas 758 ± 53 mmol/kg dry weight before the marathon anddecreased to 148 ± 39 mmol/kg dry weight immediately afterward.Despite a carbohydrate-rich diet (containing at least 7 gcarbohydrate · kg bodymass¹ · day¹),the muscle glycogen concentration remained 30% lower than before-race values 2 days after the race, whereas it had returned to before-race levels 7 days after the race. We conclude that the total GLUT-4 proteincontent is unaltered in the lateral gastrocnemius after a competitivemarathon and that the slow recovery of muscle glycogen after the raceapparently involves factors other than changes in the total content ofthis protein.

     

Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency

Caiozzo, Vincent J., Michael J. Baker, and Kenneth M. Baldwin. Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency. J. Appl.Physiol. 82(1): 211-218, 1997.This study testedthe hypothesis that mechanical loading, not stimulation frequency perse, plays a key role in determining the plasticity of myosin heavychain (MHC) protein isoform expression in muscle undergoing resistancetraining. Female Sprague-Dawley rats were randomly assigned toresistance-training programs that employed active1) shortening(n = 7) or2) lengthening contractions(n = 8). The medial gastrocnemius (MG)muscles in each group trained under loading conditions thatapproximated 90-95% of maximum isometric tetanictension but were stimulated at frequencies of 100 and~25 Hz, respectively. Lengthening and shortening contractions wereproduced by using a Cambridge ergometer system. The MG muscles trainedevery other day, performing a total of 16 training sessions. Bothtraining programs produced significant (P < 0.01) and similar reductions inthe fast type IIB MHC protein isoform in the white MG muscle, reducingits relative content to ~50% of the total MHC protein isoform pool.These changes were accompanied by increases in the relative content ofthe fast type IIX MHC protein isoform that were of similar magnitudefor both groups. The results of this study clearly demonstrate thatstimulation frequency does not play a key role in modulating MHCisoform alterations that result from high-resistance training.

     

Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice

Fahim, Mohamed A. Endurance exercise modulatesneuromuscular junction of C57BL/6NNia aging mice. J. Appl. Physiol. 83(1): 59-66, 1997.The effect ofage and endurance exercise on the physiology and morphology ofneuromuscular junctions (NMJ) of gluteus maximus muscle was studied inC57BL/6NNia mice. Mice were exercised, starting at 7 or 25 mo of age,at 28 m/min for 60 min/day, 5 days/wk for 12 wk, on a rodent treadmill.Intracellular recordings of spontaneous miniature endplate potentials(MEPP) and the quantal content of endplate potentials (EPP) wererecorded from NMJ of 10- and 28-mo-old control and exercised mice.Endurance exercise resulted in significant increases in MEPP amplitudes (23%), quantal content, and safety margin, and a significant decrease in MEPP frequency of young mice, with no change in resting membrane potential or membrane capacitance. Three months of endurance exercise resulted in an increase in MEPP frequency (41%) and decreases in MEPPamplitudes (15%), quantal content, and safety margin of old mice.Endurance exercise resulted in significantly larger nerve terminals(24%) in young animals, suggesting functional adaptation. Nerveterminals in exercised 28-mo-old mice were smaller than in thecorresponding control mice, an indication that exercise minimizedage-related nerve terminal elaboration. It is concluded that thedifferent physiological responses of young and old gluteus maximusmuscles to endurance exercise parallel their morphological responses.This suggests that the mouse NMJ undergoes a process of physiologicaland morphological remodeling during aging, and such plasticity could bemodulated differently by endurance exercise.

     

Effect of endurance exercise training on muscle glycogen supercompensation in rats

Nakatani, Akira, Dong-Ho Han, Polly A. Hansen, Lorraine A. Nolte, Helen H. Host, Robert C. Hickner, and John O. Holloszy. Effect of endurance exercise training on muscle glycogensupercompensation in rats. J. Appl.Physiol. 82(2): 711-715, 1997.The purpose of this study was to test the hypothesis that the rate and extent ofglycogen supercompensation in skeletal muscle are increased byendurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for anadditional 2 wk. Glycogen repletion was measured in trained anduntrained rats after a glycogen-depleting bout of exercise. The ratswere given a rodent chow diet plus 5% sucrose in their drinking waterad libitum during the recovery period. There were remarkabledifferences in both the rates of glycogen accumulation and the glycogenconcentrations attained in the two groups. The concentration ofglycogen in epitrochlearis muscle averaged 13.1 ± 0.9 mg/g wet wtin the untrained group and 31.7 ± 2.7 mg/g in the trained group(P < 0.001) 24 h after the exercise.This difference could not be explained by a training effect on glycogensynthase. The training induced ~50% increases in muscle GLUT-4glucose transporter protein and in hexokinase activity inepitrochlearis muscles. We conclude that endurance exercise trainingresults in increases in both the rate and magnitude of muscle glycogensupercompensation in rats.

     

Rapid reversal of adaptive increases in muscle GLUT-4 and glucose transport capacity after training cessation

Previous studies have shown that when exercise isstopped there is a rapid reversal of the training-induced adaptiveincrease in muscle glucose transport capacity. Endurance exercisetraining brings about an increase in GLUT-4 in skeletal muscle. Theprimary purpose of this study was to determine whether the rapidreversal of the increase in maximally insulin-stimulated glucosetransport after cessation of training can be explained by a similarlyrapid decrease in GLUT-4. A second purpose was to evaluate thepossibility, suggested by previous studies, that the magnitude of theadaptive increase in muscle GLUT-4 decreases when exercise training is extended beyond a few days. We found that both GLUT-4 and maximally insulin-stimulated glucose transport were increased approximately twofold in epitrochlearis muscles of rats trained by swimming for 6 h/day for 5 days or 5 wk. GLUT-4 was 90% higher, citrate synthaseactivity was 23% higher, and hexokinase activity was 28% higher intriceps muscle of the 5-day trained animals compared with the controls.The increases in GLUT-4 protein and in insulin-stimulated glucosetransport were completely reversed within 40 h after the last exercisebout, after both 5 days and 5 wk of training. In contrast, theincreases in citrate synthase and hexokinase activities were unchanged40 h after 5 days of exercise. These results support the conclusionthat the rapid reversal of the increase in the insulin responsivenessof muscle glucose transport after cessation of training is explained bythe short half-life of the GLUT-4 protein.

     

Greater airway narrowing in immature than in mature rabbits during methacholine challenge

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature thanin mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637-2643, 1996.It hasbeen demonstrated that methacholine (MCh) challenge produces a greaterincrease in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst.J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined frommeasurements of Raw in vivo and from morphometric measurements on lungsections obtained after rapidly freezing the lung after the MChchallenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greaterfor 1- and 2-mo-old animals than for 6-mo-old animals. The foldincrease in Raw was highly correlated with the degree of airwaynarrowing assessed morphometrically(r² = 0.82, P < 0.001). We conclude that thematurational difference in the effect of MCh on lung resistance isprimarily caused by greater airway narrowing in the immature rabbits.

     

Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise

The purpose of this study was to determinewhether the increase in insulin sensitivity of skeletal muscle glucosetransport induced by a single bout of exercise is mediated by enhancedtranslocation of the GLUT-4 glucose transporter to the cell surface.The rate of3-O-[³H]methyl-D-glucosetransport stimulated by a submaximally effective concentration ofinsulin (30 µU/ml) was approximately twofold greater in the musclesstudied 3.5 h after exercise than in those of the sedentary controls(0.89 ± 0.10 vs. 0.43 ± 0.05 µmol · ml¹ · 10 min¹; means ± SE forn = 6/group). GLUT-4 translocation wasassessed by using theATB-[2-³H]BMPAexofacial photolabeling technique. Prior exercise resulted in greatercell surface GLUT-4 labeling in response to submaximal insulintreatment (5.36 ± 0.45 dpm × 10³/g in exercised vs. 3.00 ± 0.38 dpm × 10³/g insedentary group; n = 10/group) thatclosely mirrored the increase in glucose transport activity. The signalgenerated by the insulin receptor, as reflected in the extent ofinsulin receptor substrate-1 tyrosine phosphorylation, was unchangedafter the exercise. We conclude that the increase in muscle insulinsensitivity of glucose transport after exercise is due to translocationof more GLUT-4 to the cell surface and that this effect is not due topotentiation of insulin-stimulated tyrosine phosphorylation.

     

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.

     

Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle

Thompson, Marita, Lisa Becker, Debbie Bryant, Gary Williams,Daniel Levin, Linda Margraf, and Brett P. Giroir. Expression ofthe inducible nitric oxide synthase gene in diaphragm and skeletal muscle. J. Appl. Physiol. 81(6):2415-2420, 1996.Nitric oxide (NO) is a pluripotent molecule thatcan be secreted by skeletal muscle through the activity of the neuronalconstitutive isoform of NO synthase. To determine whether skeletalmuscle and diaphragm might also express the macrophage-inducible formof NO synthase (iNOS) during provocative states, we examined tissuefrom mice at serial times after intravenous administration ofEscherichia coli endotoxin. In thesestudies, iNOS mRNA was strongly expressed in the diaphragm and skeletalmuscle of mice 4 h after intravenous endotoxin and was significantlydiminished by 8 h after challenge. Induction of iNOS mRNA was followedby expression of iNOS immunoreactive protein on Western immunoblots.Increased iNOS activity was demonstrated by conversion of arginine tocitrulline. Immunochemical analysis of diaphragmatic explants exposedto endotoxin in vitro revealed specific iNOS staining in myocytes, inaddition to macrophages and endothelium. These results may be importantin understanding the pathogenesis of respiratory pump failure duringseptic shock, as well as skeletal muscle injury during inflammation ormetabolic stress.