Effects of prior exercise on the action of insulin-like growth factor I in skeletal

muscle

ERIK J. HENRIKSEN, LARRY L. LOUTERS, CRAIG S. STUMP, AND CHARLES M. TIPTON Department of Exercise and Sport Sciences, University of Arizona, Tucson, Arizona 85721 Henriksen, Erik J., Larry L. Louters, Craig S. Stump, and Charles M. Tipton. Effects of prior exerciseon the action of insulin-like growth factor I in skeletalmuscle.Am. J. Physiol. 263 (Endocrinol. Met& 26): E340-E344, 1992.-Prior exercise increasesinsulin sensitivity for glucoseand system A neutral amino acid transport activities in skeletal muscle.Insulin-like growth factor I (IGF-I) also activates thesetransport processes in resting muscle. It is not known, however, whether prior exercise increasesIGF-I action in muscle. Therefore we determined the effect of a singleexhausting bout of swim exerciseon IGF-I-stimulated glucose transport activity [assessedby 2-deoxy-D-glucose (2-DG) uptake] and system A activity [assessed by ar-(methylamino)isobutyric acid (MeAIB) uptake] in the isolated rat epitrochlearis muscle.When measured3.5 h after exercise, the responsesto a submaximal concentration (0.2 nM), but not a maximal concentration (13.3 nM), of insulin for activation of 2-DG uptake and MeAIB uptake were enhanced. In contrast, prior exerciseincreasedmarkedly both the submaximal (5 nM) and maximal (20 nM) responsesto IGF-I for activation of 2-DG uptake, whereasonly the submaximal responseto IGF-I (3 nM) for MeAIB uptake wasenhancedafter exercise. We conclude that 1) prior exercise significantly enhancesthe responseto a submaximalconcentration of IGF-I for activation of the glucosetransport and systemA neutral amino acid transport systemsin skeletal muscleand 2) the enhanced maximal responsefor IGF-I action after exerciseis restricted to the signaling pathway for activation of the glucosetransport system. 2-deoxy-D-glucoseuptake; ac-(methylamino)isobutyricacid uptake; swim exercise;insulin action; epitrochlearis muscle IT IS WELL DOCUMENTED that, after an intense bout of exercise, the insulin sensitivity of skeletal muscle glucose transport activity (2, 8, 17, 18, 25, 26, 30) and system A neutral amino acid transport activity (28, 30) is increased. The enhanced effect of insulin in stimulating the glucose transport process is evident only after the elevated rate of insulin-independent glucose transport has partially or completely reversed (8, 17, 25, 30). In skeletal muscle, glucose transport and system A amino acid transport activities can also be stimulated by insulin-like growth factor I (IGF-I) (4, 5, 10, 15, 16, 22, 27). IGF-I is a 70.amino acid peptide that shares a high degree of sequence homology with insulin (5, 19). In skeletal muscle, significant numbers of IGF-I receptors are detectable (4, 12, 22, 31), and in this tissue insulin and IGF-I are thought to mediate their stimulatory effects on glucose transport via their individual receptor systems (4, 5, 15, 16, 22). Indeed, Dohm et al. (4) demonstrated, using displacement studies of purified skeletal muscle insulin and IGF-I receptors, that insulin has a very low affinity for the IGF-I receptor and that IGF-I has a very low affinity for the insulin receptor. However, insulin and IGF-I probably mediate their effects on skeletal muscle glucose transport by a shared intracellular mechanism, because the maximal effects of these hormones on this process are not additive (15, 20). E340

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It is not currently known whether IGF-I action on glucose and system A amino acid transport processes in skeletal muscle is enhanced by prior exercise, as is the case for insulin (2, 8, 17, 18, 25, 26, 29, 30). Therefore the purpose of this study was to characterize and compare the effects of a single bout of exhaustive swim exercise on the actions of insulin and IGF-I, at either submaximally or maximally effective concentrations, in the isolated epitrochlearis muscle. Two independent sarcolemmal transport processes were measured in vitro 3.5 h after exercise as follows: glucose transport activity, assessed using the glucose analogue 2-deoxy-D-glucose (2,DG), and system A neutral amino acid transport activity, assessed using a-(methylamino)isobutyric acid (MeAIB), which is specific for system A (3, 21). MATERIALSAND METHODS Materials. Purified porcine insulin was obtained from Eli Lilly (Indianapolis, IN), and IGF-I was a generousgift of Lilly ResearchLabs (Indianapolis, IN). 2-DG, MeAIB, bovine serum albumin (BSA), and all other biochemicals were purchased from Sigma (St. Louis, MO). 2-Deoxy-[1,2-3H]glucosewasfrom Sigma and [l*C]mannitol was from ICN Radiochemicals (Irvine, CA). Animals and swimexercise. Male Wistar rats (Sasco,Omaha, NE) weighing loo-120 g were used in all experiments. Food (Purina Rat Chow) wasrestricted to 4 g/animal at 5:00 P.M. the evening before the experiment. At 9:00 A.M., rats wereexercised by swimmingin a plastic barrel (water 50 cm in depth, 53 cm in diameter, and kept at 35°C) as describedby Young et al. (26). Briefly, a maximum of eight rats per barrel (averagesurfacearea per rat was276 cm2)were exercisedinitially for 30 min. Thereafter, 1.5%of body weight wasaddedto the tail of eachrat, and two further 30-min sessionsfollowed by a final 60-min session were completed.Sessionswere separatedby 5-min rest periods, during which rats were placed on a dry towel in a plastic tub. This exerciseprotocol causesmarked glycogen depletion of the epitrochlearis muscle (25% or less of initial) and maximally activates insulin-independent glucosetransport in this muscle (2, 8, 25, 26). Muscle preparation. Sedentary and exercisedanimals (after completing the final swim bout) were anesthetizedwith an intraperitoneal injection of pentobarbital sodium (5 mg/lOO g body wt). Both epitrochlearismuscleswerequickly removedand treated as described below. The epitrochlearis muscle from these animals weighs -20 mg and is an excellent preparation for in vitro incubations of 9 h or more (6, 7, 13). Muscle incubations. For the initial studies of the doseresponserelationships for IGF stimulation of 2-DG uptake and MeAIB uptake in the epitrochlearis, muscleswere incubatedat 37°C for 30 min in Krebs-Henseleitbuffer (KHB; seeRef. 11) containing either 2 mM sodiumpyruvate and 36 mM mannitol (glucosetransport study) or 5 mM glucoseand 1 mM mannitol (systemA amino acid transport study), 0.1% BSA (radioimmunoassaygrade), and various concentrations of IGF-I. The uptake of 2-DG or MeAIB wasthen measuredas describedbelow. For the exercisestudies,epitrochlearis muscleswere incubated at 37°C for 3 h in stopperedErlenmeyer flasks containing 2 ml the AmericanPhysiological Society

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KHB supplemented with either 8 mM glucose and 32 mM mannitol (glucose transport study) or 5 mM glucose and 1 mM mannitol (system A amino acid transport study). This incubation period has been shown to be necessary for the acute insulin-independent effects of swim exercise on glucose transport to decline and to allow the increased action of insulin on this process to become evident (25, 26). The gas phase in the flasks was 95% 02-5% CO,. After this initial incubation period, the muscles were transferred to fresh KHB containing either 2 mM pyruvate and 36 mM mannitol (glucose transport study) or 5 mM glucose and 1 mM mannitol (system A amino acid transport study), 0.1% BSA, and either no other additions, insulin, or IGF-I, as indicated (see Tables l-4 and Figs. 1 and 2). Measurement of Z-DG uptake. Glucose transport activity was measured using the glucose analogue 2-DG. Muscles were incubated for 20 min at 37°C in 1.5 ml KHB containing 1 mM 2-deoxy-[1,2-c3H]glucose (300 &i/mmol) and 39 mM [U-14C]mannitol (0.8 &i/mmol), in the absence or presence of the additions indicated. The gas phase in the flasks was 95% 02-5% CO,. The muscles were then blotted on filter paper moistened with ice-cold medium, trimmed, and quickly frozen between aluminum blocks cooled in liquid N,. After weighing, muscles were placed in scintillation vials containing 0.5 ml of 0.5 N NaOH. After complete solubilization of the muscles, 5 ml of scintillation cocktail were added, and the samples were counted for radioactivity in the 13H and i4C channels using a Beckman model LS5801 liquid scintillation counter with automatic external standardization to correct for quenching. All values for 2-DG uptake are expressed as picomoles of 2-DG per milligram muscle wet weight per 20 min. Measurement of system A amino acid uptake. System A amino acid uptake was measured using the nonmetabolizable analogue MeAIB, according to the procedure of Guma et al. (9). Muscles were incubated for 30 min at 37°C in flasks containing 1.5 ml KHB supplemented with 5 mM glucose, 0.1 mM CY-[~“C]MeAIB (400 &i/mmol), 1 mM [“Hlmannitol (165 &i/mmol), in the absence or presence of insulin or IGF-I, as indicated. The muscles were then frozen and processed exactly as described above for 2-DG uptake. The specific uptake of MeAIB was calculated as described by Henriksen (10). All values for MeAIB uptake are expressed as picomoles of MeAIB per milligram muscle wet weight per 30 min. Statistics. All data are expressed as means & SE. Differences in absolute transport rates between sedentary and exercise groups within a table were tested for statistical significance by analysis of variance with a post hoc Scheffe F test. Differences between a sedentary group and an exercise group for the increased transport rate above basal at a given hormone concentration were analyzed by an unpaired Student’s t test. Probability levels of ~0.05 were considered statistically significant.

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Table 1. Effect of prior swim exercise on stimulation of 2-deoxyglucose uptake in epitrochlearis muscle by insulin pmol * mg muscleInsulin,

nM

2-Deoxyglucose uptake

l- 20 min-

Increase due to insulin

n

Sedentary 252t22 6 6 407t49 330228 6 6 1,088t86 3.5 h After Exercise 48&33 8 1,065t95* 8 398t36 7 7 1,308_t131

0 0.2 0 13.3 0 0.2 0 13.3

l n

155k43

6

758k64

6

578t75*

8

910t119

7

Values are means t SE; n, no. of muscles. One muscle from each animal was incubated in absence of hormone, while contralateral muscle was treated with indicated concentration of hormone. In this way, an absolute increase due to hormone could be calculated for each animal, and group means for these absolute increases could be statistically compared. * P < 0.001 vs. sedentary + 0.2 nM insulin.

response to a maximally effective concentration of insulin (13.3 nM) did not differ significantly between exercise and sedentary groups (Table 1). These findings regarding postexercise insulin-stimulated glucose transport activity, measured using 2-DG, are essentially the same as those of previous investigations using a similar muscle preparation and the nonmetabolizable glucose analogue 3-0-methylglucose (8, 25, 26). Because IGF-I action on 2-DG uptake in the isolated epitrochlea ris has not been characterized, we initially established a dose-response curve using mu scles from sedentary animals (Fig. 1). A maximal-response for 2-DG uptake was found at IGF-I concentrations 220 nM, while the ECSO was 4 nM. As presented in Table 2, IGF-I action on stimulation of 2-DG uptake was enhanced 3.5 h after exercise. In response to a submaximally effective concentration of IGF-I (5 nM), the increase in 2-DG uptake above basal

RESULTS

Effect of exercise on insulin- or IGF-I-stimulated glucose transport activity. Our initial experiments were de-

signed to confirm that, under the conditions employed the glucose analogue 2DG, an acute bout of exhaustive exercise would result in an enhanced response to insulin for glucose transport by the epitrochlearis muscle (8, 25, 26). As shown in Table 1, 3.5 h after exercise the basal rate of 2-DG uptake was still elevated relative to control, although these differences did not achieve statistical significance. Nevertheless, the increase in 2-DG uptake above basal in response to a submaximal dose of insulin (0.2 nM) was significantly greater in the exercised group compared with the control group (Table 1). On the other hand, the increase above basal for 2-DG uptake in

using

01’

r

” 0

” 10

’ 20

l 30



’ 40

J 50

IGF-I, nM

Fig. 1. Dose-response relationship for insulin-like growth factor I (IGFI)-stimulated 2-deoxyglucose (2-DG) uptake in epitrochlearis muscles. Epitrochlearis muscles were removed from sedentary animals and incubated for 30 min in buffer containing various concentrations of IGF-I. 2-DG uptake was then determined as described in MATERIALS AND METHODS. Each point represents mean t SE for 5-14 muscles.

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Table 2. Effect of prior swim exercise

MUSCLE

r

on stimulation of 2-deoxyglucose uptake in epitrochlearis muscle by IGF-I pm01 +mg muscle-l. IGF-I,

nM

2 -Deoxyglucose uptake

n

20 min-l Increase due to IGF-I

n

Sedentary 0 5 0 20

243t28 623t34 275t15 765&39

6 6 6 6

3.5 h After 375k37 1,148+77t 402k28 1,268+69t

0 5 0 20

Exercise 8 8 8 8

38Ok42

6

489t45

6

773t99*

8

866&613

8

Values are means & SE; n, no. of muscles. See Table 1 for explanation of experimental design. * P c 0.005, t P < 0.001 vs. sedentary + insulin-like growth factor I (IGF-I) at same concentration.

was significantly greater in the exercise group than in the sedentary control group. The response of the previously exercised group to a maximally effective concentration of IGF-I (20 nM) was also significantly greater than that of the control muscles. Effect of exercise on insulin- or IGF-I-stimulated system A actiuity. The effect of an acute bout of swim exercise on

insulin-stimulated system A neutral amino acid transport activity has not been investigated using the isolated epitrochlearis muscle. Therefore we initially assessed insulin action on system A activity, as measured by MeAIB uptake, after swim exercise (Table 3). Basal MeAIB uptake did not differ between sedentary and exercise groups. In response to a submaximally effective concentration of insulin (0.2 nM), MeAIB uptake was increased to a significantly greater rate in the exercise group compared with the sedentary control group. In contrast, neither the rates of MeAIB uptake nor the absolute increases above basal achieved in the presence of a maximally effective concentration of insulin (13.3 nM) differed significantly between groups. As was the case with glucose transport activity (Fig. l), it was also necessary to characterize the dose-response relationship for IGF-I stimulation of MeAIB uptake in Table 3. Effect of prior swim exercise on stimulation of MeAIB uptake in epitrochlearis muscle by insulin pm01 . mg muscle-l Insulin,

0

I

I

I

I

15

20

25

30

IGF-I, nM

Fig. 2. Dose-response relationship for IGF-I-stimulated a-(methylamino)isobutyric acid (MeAIB) uptake in epitrochlearis muscles. Epitrochlearis muscles were removed from sedentary animals and incubated for 30 min in buffer containing various concentrations of IGF-I. MeAIB uptake was then determined as described in MATERIALS AND METHODS. Each point represents mean t SE for 4-6 muscles.

the epitrochlearis (Fig. 2). From this dose-response curve, we established that 3 and 20 nM IGF-I were submaximally and maximally effective concentrations, respectively, for activation of MeAIB uptake in this muscle. The effect of IGF-I on the stimulation of MeAIB uptake after exercise is shown in Table 4. A submaximal concentration of IGF-I (3 nM) increased MeAIB uptake to a significantly greater rate in the exercise group relative to control, and the absolute increase of MeAIB uptake above basal due to this dose of IGF-I was also greater in the exercise group. In contrast, the rates of MeAIB uptake in the two groups after treatment with a maximally effective concentration of IGF-I (20 nM) were not significantly different, although the absolute increase above basal due to 20 nM IGF-I was statistically greater in the exercise group compared with the sedentary control group. DISCUSSION

The most striking and important finding of the present study was that prior exercise increased the response to Table 4. Effect of prior swim exercise on stimulation of MeAIB uptake in epitrochlearis muscle by IGF-I pm01 . mg muscle-l IGF-I,

uptake

I 10

- 30 min-l

nM MeAIB

I 5

Increase

nM MeAIB

due to insulin

Sedentary 0 0.2 0 13.3

30.8k2.0 53.324.3 39.0t3.3 119&B

0 0.2 0 13.3

3.5 h After 37.8t3.9 84.9k5.67 44.2t6.4 137kll

n

uptake

v30 min-I Increase due to IGF-I

n

Sedentary 22.5t3.2 80.2k8.3

0 3 0 20

36.8t2.7 46.2k3.9 37.7k3.2 67.0k4.9

0 3 0 20

3.5 h After 40.624.0 73.8t8.0” 36.2t2.8 78.1t4.4

Exercise 47.1k5.4” 92.8k6.5

Values are means t SE; n = 6 muscles. MeAIB, cr-(methylamino)isobutyric acid. See Table 1 for explanation of experimental design. * P < 0.01, t P c 0.001 vs. sedentary + 0.2 nM insulin.

5 5 6 6 Exercise 7 7 7 7

9.422.7

5

29.222.7

6

33.2+6.1$

7

41.9+4.1?

7

Values are means t SE; n, no. of muscles. See Table 1 for explanation of experimental design. * P < 0.05, t P c 0.02, $ P < 0.01 vs. sedentary + IGF-I at same concentration.

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IGF-I for stimulation of glucose transport activity in the epitrochlearis. The effect of IGF-I on stimulation of 2-DG uptake was enhanced at both submaximal (5 nM) and maximal (20 nM) concentrations after exercise (Table 2). In epitrochlearis muscles from sedentary animals, although the rate of 2-DG uptake stimulated by 20 nM IGF-I was only -70% of the rate elicited by maximal insulin, the rate of 2-DG uptake achieved in exercised muscles stimulated by 20 nM IGF-I was not statistically different from that rate observed in exercised muscles stimulated with 13.3 nM insulin (1,268 t 69 vs. 1,308 t 131 pmolmg muscle-l 20 min-‘; Tables 1 and 2). IGF-I can now be added to the growing list of compounds whose action on glucose transport is enhanced after vigorous exercise (1). The effect of prior exercise on IGF-I-stimulated system A neutral amino acid transport differed from its effect on the glucose transport system. Exercise significantly increased the response to a submaximally effective concentration of IGF-I for stimulation of MeAIB uptake, so that it was not different from the rate achieved with a maximally effective IGF-I concentration (Table 4). In addition, the rates of MeAIB uptake after treatment with a maximal dose of IGF-I were not statistically different between sedentary and exercise groups (Table 4). However, this apparent maximal capacity for IGF-I-stimulated MeAIB uptake is much less than the rate achieved with 13.3 nM insulin (Table 3). These observations suggest that an acute bout of swim exercise specifically enhances IGF-I responsiveness for stimulation of glucose transport activity, but not for system A activity, possibly by allowing the signal produced by the IGF-I receptor to access a component of the insulin-stimulatable glucose transport pathway that is normally not used in resting muscle. Using 2-DG as the glucose analogue, we have confirmed previous findings using 3-0-methylglucose (8,25,26) that the response to submaximally effective, but not a maximally effective, dose of insulin for activation of glucose transport is markedly enhanced in the epitrochlearis muscle 3.5 h after an acute bout of exhaustive swim exercise (Table 1). In addition, the results of the present study indicate that swim exercise induces a similar increase in the action of a submaximal insulin concentration for system A neutral amino acid transport (Table 3). Although some of the enhanced effects of IGF-I after exercise may be the result of IGF-I interaction with the insulin receptor binding site, it is likely that this is not the sole mechanism for this effect. First, previous studies have documented that, in skeletal muscle, IGF-I binding to the insulin receptor is very limited (4, 5, 15, 16, 22). Second, if cross-reactivity were indeed the sole mechanism, then one would expect that IGF-I responsiveness of MeAIB uptake (Table 4) would have increased to a similar extent as IGF-I responsiveness of 2-DG uptake (Table 2), which was clearly not the case. The majority of IGF-I in serum is complexed with both high-molecular-weight (150,000) and low-molecularweight (34,000) IGF binding proteins (IGFBPs), and the modulation of IGF action in peripheral tissues by these IGFBPs has been the subject of numerous recent invesl

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tigations (for a review see Ref. 14). Prolonged exercise causes a marked increase in the serum level of the 34,000 IGFBP (23). How this increase in IGFBPs during exercise modulates IGF-I action on glucose transport and system A amino acid transport activities in skeletal muscle during recovery from exercise is unknown. Nevertheless, the possibility exists that alterations in IGFBP levels, both in the serum and in muscle itself, may account for at least some of the increases in IGF-I action after exercise. In the present study, we have shown for the first time that the epitrochlearis, a skeletal muscle consisting of predominantly fast glycolytic fibers (13), is highly responsive to the action of IGF-I for stimulation of both glucose transport activity (Fig. 1) and system A neutral amino acid transport activity (Fig. 2). In epitrochlearis muscles from sedentary animals, IGF-I was only -6O70% as potent as insulin in maximally stimulating these membrane transport processes (Tables l-4). This conflicts with the finding of previous investigations (22, 27) that insulin and IGF-I stimulate 2-DG uptake to the same maximal level in the soleus. However, we have also observed in the isolated soleus strip preparation that 20 nM IGF-I stimulates 2-DG uptake to only -75% of the level achieved in response to 13.3 nM insulin (E. J. Henriksen and L. S. Ritter, unpublished observations). The reason for this discrepancy remains to be determined. As recently reported by Gulve et al. (6, 7) in the epitrochlearis and by Tovar et al. (24) in the soleus, prolonged incubation of muscles leads to increased basal and insulin-stimulated glucose and system A amino acid transport activities. In the present study, we observed that 3.5 h of incubation resulted in no increases or minimal increases in basal, insulin-, or IGF-I-stimulated 2-DG uptake (Tables 1 and 2) relative to those rates measured after 0.5 h of incubation (Fig. 1 and unpublished data). On the other hand, this extended incubation period caused substantial increases (+35-60%) in basal, insulin-, and IGF-I-stimulated rates of MeAIB uptake (Tables 3 and 4) relative to incubations of 0.5 h or less (Fig. 2; Ref. 10). Therefore this effect of incubation time affects the system A neutral amino acid transport system more rapidly than the glucose transport system (6, 7). However, this effect of incubation should not be seen as a confounding factor in the interpretation of our MeAIB uptake data, because the increases appeared to be manifested equally in all groups (Tables 3 and 4). In conclusion, our results confirm that a single bout of exhausting swim exercise increases the action of a submaximal dose of insulin on skeletal muscle glucose transport and system A neutral amino acid transport systems, with no major changes in the maximal responses. More importantly, we have documented for the first time that exercise also significantly increases the action of IGF-I on these sarcolemmal transport processes in skeletal muscle. However, the increase in the IGF-I responsiveness after swim exercise appears to be restricted to the glucose transport system. These findings suggest that exercise increases the maximal capacity of IGF-I action on glucose transport, possibly by increasing the ability of IGF-I to

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interact with the intracellular pathways and/or IGF-I-stimulated glucose transport.

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28 October

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17.

18.

1992. 19.

REFERENCES 1. Cartee, G. D., and J. 0. Holloszy. Exercise increases susceptibility of muscle glucose transport to activation by various stimuli. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E390-E393, 1990. 2. Cartee, G. D., D. A. Young, M. D. Sleeper, J. R. Zierath, H. Wallberg-Henriksson, and J. 0. Holloszy. Prolonged increase in insulin-stimulated glucose transport in muscle after exercise. Am. J. Physiol. 256 (Endocrinol. Metab. 19): E494-E499, 1989. 3. Christensen, H. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol. Rev. 70: 43-77, 1990. 4. Dohm, G. L., C. W. Elton, M. S. Raju, N. D. Mooney, R. DiMarchi, W. J. Pories, E. G. Flickinger, S. M. Atkinson, and J. F. Caro. IGF-I-stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM. Diabetes 39: 1028- 1032, 1990. 5. Froesch, E. R., C. Schmid, J. Schwander, and J. Zapf. Actions of insulin-like growth factors. Annu. Rev. Physiol. 47: 443-467, 1985. 6. Gulve, E. A., G. D. Cartee, and J. 0. Holloszy. Prolonged incubation of skeletal muscle in vitro: prevention of increases in glucose transport. Am. J. Physiol. 261 (Cell Physiol. 30): C154C160, 1991. 7. Gulve, E. A., G. D. Cartee, J. H. Youn, and J. 0. Holloszy. Prolonged incubation of skeletal muscle increases system A amino acid transport. Am. J. Physiol. 260 (Cell Physiol. 29): C88-C95, 1991. 8. Gulve, E. A., G. D. Cartee, J. R. Zierath, V. M. Corpus, and J. 0. Holloszy. Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose. Am. J. Physiol. 259 (Endocrinol. Metab. 22): E685-E691, 1990. 9. Guma, A., X. Testar, M. Palacin, and A. Zorzano. Insulinstimulated cr-(methyl)-aminoisobutyric acid uptake in skeletal muscle. Biochem. J. 253: 625-629, 1988. 10. Henriksen, E. J. Effects of phenylarsine oxide on insulin-stimulated system A amino acid uptake in skeletal muscle. Am. J. Physiol. 261 (Cell Physiol. 30): C608-C613, 1991. 11. Krebs, H. A., and K. Henseleit. Untersuchung uber die Harnstoffbildung im Tierkorper. Hoppe-Seyler’s 2. Physiol. Chem. 210: 33-66, 1932. N., T. Pollare, H. Lithell, and P. Arner. Char12. Livingston, acterization of insulin-like growth factor I receptor in skeletal muscles of normal and insulin resistant subjects. Diabetologia 31: 871-877, 1988. R., I. E. Karl, K. K. Kaiser, and D. M. Kipnis. 13. Nesher, Epitrochlearis muscle. I. Mechanical performance, energetics, and fiber composition. Am. J. Physiol. 239 (Endocrinol. Metab. 2): E454-E460, 1980.

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14. Ooi, 15.

We thank Leslie S. Ritter and Patti L. Naeger for excellent technical assistance. We also acknowledge the generous gift of IGF-I from Lilly Research Labs, Indianapolis, IN. This work was supported in part by Grant BRSG S07RR07002, awarded by the Biomedical Research Support Grant Program, Division of Research Resources, National Institutes of Health, by Grant-in-Aid IG-Z-10-91 from the Arizona Affiliate of the American Heart Association, and by Grant NAG2392 and Graduate Student Researchers Program Award NGT-50493 from the National Aeronautics and Space Administration. Address for reprint requests: E. J. Henriksen, Dept. of Exercise and Sport Sciences, McKale Center 228A, Univ. of Arizona, Tucson, AZ 85721. Received

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28.

29.

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Effects of prior exercise on the action of insulin-like growth factor I in skeletal muscle.

Prior exercise increases insulin sensitivity for glucose and system A neutral amino acid transport activities in skeletal muscle. Insulin-like growth ...
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