Journal of Applied Physiology Millar Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 81: 1924-1928, 1996;
8750-7587/96 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Asp, S.
Right arrow Articles by Richter, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Asp, S.
Right arrow Articles by Richter, E. A.

Journal of Applied Physiology
Vol. 81, No. 5, pp. 1924-1928, November 1996
EXERCISE AND MUSCLE

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

Sven Asp and Erik A. Richter

Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES

ABSTRACT

Asp, Sven, and Erik A. Richter. Decreased insulin action on muscle glucose transport after eccentric contractions in rats. J. Appl. Physiol. 81(5): 1924-1928, 1996.---We have recently shown that eccentric contractions (Ecc) of rat calf muscles cause muscle damage and decreased glycogen and glucose transporter GLUT-4 protein content in the 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 [Medline] ). To study whether these changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 µU/ml) 2 days after one-legged eccentric contractions of the calf muscles. Compared with control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG, whereas it was lower (P < 0.05) at both submaximal and maximal insulin concentrations in the Ecc-WG and at maximal concentrations in the Ecc-RG. In the Ecc-S, the glucose transport was unchanged in hindquarters perfused in the absence or presence of a submaximal stimulating concentration of insulin, whereas it was slightly (P < 0.05) higher during maximal insulin stimulation compared with control S. At the end of perfusion the glycogen concentrations were lower in both Ecc-gastrocnemius muscles compared with control muscles at all insulin concentrations. Fractional velocity of glycogen synthase increased similarly with increasing insulin concentrations in Ecc- and control WG and RG. We conclude that insulin action on glucose transport but not glycogen synthase activity is impaired in perfused muscle exposed to prior eccentric contractions.

skeletal muscle; insulin resistance

INTRODUCTION

A SINGLE BOUT of concentric exercise (which involves shortening of active muscle) is a recognized enhancer of insulin action systemically and in muscle in rats and humans (7, 19, 21, 22), whereas it has been reported that a bout of eccentric exercise (which involves forced lengthening of active muscle) transiently impairs whole body insulin action 2 days after the bout (16). The underlying mechanism(s) for this apparent insulin-resistant state remains obscure, but both local and/or systemic changes are possible. In recent studies in humans and rats, we showed that eccentric contractions induce a transient decrease in the skeletal muscle glucose transporter isoform (GLUT-4) protein content (4, 5). GLUT-4 is the predominant glucose transporter in skeletal muscle fibers (17), and translocation of GLUT-4 from an intracellular pool to the sarcolemma and t-tubules occurs by insulin stimulation (12, 13, 29). Because insulin-induced glucose transport (15) and uptake (1, 10) have been found to correlate with muscle GLUT-4 content, decreased GLUT-4 content could be part of the explanation for the insulin resistance found systemically. Also, this could be part of the reason for the sustained low muscle glycogen concentration after eccentric contractions (6, 9, 11, 20, 28). Thus, in the present study, we used the perfused rat hindquarter technique to investigate whether eccentric damage decreases insulin's ability to stimulate muscle glucose transport and glycogen synthase activity. Because we previously showed that muscle GLUT-4 protein content was decreased maximally 2 days after eccentric contractions (5), insulin action on glucose transport and glycogen synthase activity was studied in muscle perfused 2 days after eccentric muscle contractions.

MATERIALS AND METHODS

Animals and diets. All experiments were approved by the Danish Animal Experiments Inspectorate and complied with the "European Convention for the Protection of Vertebrate Animals Used for Experiments and Other Scientific Purposes" (Council of Europe no. 123, Strasbourg, France, 1985). Male Wistar rats weighing ~200-240 g were housed three per cage on a 12:12-h light-dark cycle and were fed on an ad libitum standard chow diet (Altromin no. 1324, Petersen, Ringsted, Denmark; 62% energy intake as carbohydrate), which was maintained until the end of the experiment.

Eccentric contraction model. Rats were anesthetized by an intraperitoneal injection of Dormicum (midazolam, 0.5 µg/kg body wt; Roche, Switzerland) and Hypnorm (fentanyl, 20 µg/kg body wt, and fluoanison, 1 mg/kg body wt; Janssen), and the calf muscles on one side were stimulated for eccentric contractions (Ecc-muscles) as described previously (5), whereas the contralateral muscles were unstimulated controls. In brief, muscles were subjected to 4 × 10 eccentric contractions with 1 min of rest between the 4 series. Stimulation sessions were carried out between 0800 and 1200, and after recovery from anesthesia the gait of the rats appeared completely normal.

Hindquarter perfusion. Two days after the stimulation the rats were anesthetized by an intraperitoneal injection of pentobarbital sodium (5 mg/100 g body wt) and prepared for hindquarter perfusion as described by Ruderman et al. (25) modified for male rats. Before insertion of the perfusion catheters, the rat was heparinized with 500 IU heparin in the inferior vena cava. The rat was killed by an intracardial injection of pentobarbital sodium just before being placed in the perfusion cabinet. The perfusion apparatus was similar to that described previously (24). The perfusate consisted of Krebs-Henseleit solution, 1- to 2-day-old bovine erythrocytes, 5% bovine serum albumin, 10 mM glucose, and 0.5-1.0 mM lactate originating from the erythrocytes. Human insulin was present in the perfusate at 0, 200, or 20,000 µU/ml cell-free perfusate from the beginning of the perfusion. The perfusate was continuously gassed with a mixture of 3% CO2-35% O2-62% N2. To ensure a perfusate temperature of 37°C, the perfusate was warmed in a water-perfused heating coil (37°C) immediately before entering the hindquarter. The first 25 ml of perfusate that passed through the hindquarter were discarded, and then the perfusate was recirculated. The initial volume of perfusate was 300 ml. To allow equilibration, the hindquarter was preperfused and then the actual experimental period began. When insulin was omitted from the perfusate (basal), the hindquarters were preperfused for 10 min and the experimental period, where tracer was added to the perfusate, was 30 min. In the experiments with insulin at 200 µU/ml (submaximal), the hindquarters were preperfused for 15 min followed by a 15-min experimental period and finally the experiments with insulin at 20,000 µU/ml (maximal); the preperfusion period was 15 min followed by a 10-min experimental period. The different exposure times for the isotopes were constructed to obtain intramuscular concentrations of 3-O-methyl-D-glucose of <30% of the cell-free perfusate concentration to avoid nonlinearity of uptake. At the end of perfusion, the pump was stopped and muscle samples were cut out, trimmed of connective tissue and visible blood, and blotted. The superficial part of the gastrocnemius (WG) muscle, which consists mainly of fast-twitch white fibers (2), the soleus (S) muscle, which consists mainly of slow-twitch fibers (2), and, finally, a portion of the deep part of the medial head of the gastrocnemius (RG) muscle, consisting mainly of fast-twitch red fibers (2), were cut out. The muscle samples were freeze clamped with tongs cooled in liquid nitrogen and stored at -80°C until analyzed.

For measurement of muscle membrane glucose transport, 10-20 µCi of 3-O-[methyl-14C]-methyl-D-glucose (specific activity 315 mCi/mmol; New England Nuclear, Boston, MA) along with 20 µCi [3H]mannitol (specific activity 22.5 Ci/mmol; New England Nuclear) were added at the start of the actual experimental period. Also, cold mannitol yielding a perfusate concentration of 1 mM was added simultaneously. Because transit time from the reservoir to the hindquarter was 2.75 min, the hindquarters were exposed to isotopes for 27.25, 12.25, or 7.25 min, at basal, submaximal, and maximal insulin concentrations, respectively. Muscle glycogen was measured by a hexokinase method after acid hydrolysis (18). Glycogen synthase activity was measured with a modification of the filter paper method of Thomas et al. (27), where maximal activity was measured at saturating (8 mM) glucose 6-phosphate concentration and the percent fractional velocity was calculated as activity at a submaximal glucose 6-phosphate concentration (0.17 mM) in percentage of maximal activity. Total water content of muscle was determined by weighing before and after lyophilization for 48 h.

Glucose transport. Uptake of 3-O-methyl-D-glucose in the individual muscles was determined in perchloric acid extracts and corrected for label in the extracellular space determined by the 3H counts for mannitol. From the uptake of labeled 3-O-methyl-D-glucose, rates of glucose transport were calculated by using a specific activity of glucose determined by the glucose concentration in the cell-free arterial perfusate and the 3-O-methyl-D-glucose counts. To compare transport rates into muscles despite differences in mannitol space in control and Ecc-muscles, transport was expressed as micromoles of glucose per gram of non-mannitol-accessible muscle per hour, and for this calculation we used an equation derived from Richter et al. (23), assuming the mass density of the mannitol space being 1 g/ml
C<SUB>nma</SUB> = (C<SUB>m</SUB> − C<SUB>p</SUB> &z.ccirf; E) &z.ccirf; W &z.ccirf; (W−E)<SUP>−1</SUP> &z.ccirf; T<SUP>−1</SUP>
where Cnma is glucose transport rate (in µmol glucose · g of non-mannitol-accessible muscle-1 · h-1), Cm is glucose concentration in muscle calculated from 3-O-[methyl-14C]-methyl-D-glucose counts in muscle, with the assumption of the same specific activity in muscle and plasma (µmol glucose/g wet wt muscle), Cp is glucose concentration in perfusate plasma water (µmol glucose/ml perfusate plasma water), E is extracellular (mannitol) space (ml/g wet wt muscle), W is muscle weight (g wet wt), and T is time that muscles are exposed to tracers (h).

Statistics. Mean values from control and Ecc-muscles were compared by Student's paired t-test. To compare mean glycogen values at the different insulin concentrations, a one-way analysis of variance was used. Student's unpaired t-test was used as post hoc test.

RESULTS

Compared with the control muscle, basal glucose transport rate was slightly higher in the Ecc-WG and -RG but not in the Ecc-S (Fig. 1). Insulin-stimulated glucose transport was impaired in the Ecc-WG both at submaximal and maximal insulin concentrations (Fig. 1A). In the Ecc-RG, the maximal transport rate was lower compared with control muscle, whereas at submaximal insulin concentrations there was no significant difference (Fig. 1B). In the Ecc-S, maximal insulin-stimulated glucose transport surprisingly was slightly but significantly higher compared with control muscle (Fig. 1C).

Fig. 1. Glucose transport in calf muscles 2 days after one-legged eccentric contractions. Values are means ± SE of 7-9 observations in each group. When no SE is shown, it is contained within the symbols. A: white gastrocnemius. B: red gastrocnemius. C: soleus. Open symbols, control muscles; solid symbols, eccentrically stimulated muscles. * Significantly different from control, P < 0.05.
[View Larger Version of this Image (13K GIF file)]

The muscle glycogen concentration at the end of the perfusions was lower in the Ecc-WG and -RG, whereas in the Ecc-S the glycogen concentration was similar to the corresponding control leg at all insulin concentrations (Table 1). In control muscle, glycogen concentrations at the end of perfusion were significantly higher when insulin was present in the perfusate than when it was absent. This was also the case in the Ecc-RG and -S but not in the Ecc-WG, in which no net insulin-stimulated glycogen synthesis was apparent (Table 1).

Table 1. Glycogen in calf muscles 2 days after one-legged eccentric contractions

Insulin, µU/ml
0 200 20,000
WG-C 197.7 ± 14.4  238.6 ± 9.1dagger 238.0 ± 8.4dagger
Ecc-WG 132.0 ± 6.1* 134.1 ± 16.6* 141.0 ± 6.7*
RG-C 213.8 ± 16.3  255.6 ± 11.4dagger 275.7 ± 9.7dagger
Ecc-RG 137.8 ± 17.7* 180.8 ± 11.1*dagger 191.1 ± 7.1*dagger
S-C 151.0 ± 10.3  188.2 ± 8.7dagger 215.6 ± 10.2dagger
Ecc-S 152.9 ± 10.1  187.2 ± 10.8dagger 209.5 ± 9.0dagger
Values are means ± SE of 7-9 observations in each group given in mmol/kg dry wt. WG-C, control white gastrocnemius; Ecc-WG, eccentrically stimulated white gastrocnemius; RG-C, control red gastrocnemius; Ecc-RG, eccentrically stimulated red gastrocnemius; S-C, control soleus; Ecc-S, eccentrically stimulated soleus. * Significantly different from control value, P < 0.05.  dagger Significantly different from basal (0 µU/ml insulin) value, P < 0.05.

The fractional velocity of glycogen synthase increased with increasing insulin concentrations in WG and not significantly in RG, and there were no differences between Ecc- and control muscles (Table 2). The maximal activity of glycogen synthase was on average 16% lower in the Ecc-WG compared with control, whereas it was unaffected in the Ecc-RG (Table 2).

Table 2. Glycogen synthase fractional velocity and maximal activity in calf muscles 2 days after one-legged eccentric contractions

Insulin, µU/ml
Average
0 200 20,000
GS fractional velocity, % 
  WG-C 30.4 ± 2.5  38.7 ± 3.8  42.7 ± 2.1dagger
  Ecc-WG 28.0 ± 0.9  36.7 ± 2.8dagger 42.8 ± 2.2dagger
  RG-C 30.1 ± 4.3  34.2 ± 3.3  40.4 ± 2.7 
  Ecc-RG 30.8 ± 3.6  32.7 ± 4.6  37.5 ± 3.6 
GS maximal activity, nmol · min-1 · mg dry wt-1
  Ecc-WG 11.1 ± 1.1  12.7 ± 0.8  12.0 ± 0.7  11.9 ± 0.5 
  WG-Ecc 8.7 ± 1.0* 12.1 ± 1.3  9.7 ± 0.9* 10.0 ± 0.6*
  RG-C 13.0 ± 1.2  10.8 ± 1.8  11.9 ± 1.4  11.0 ± 0.8 
  Ecc-RG 10.1 ± 0.8  9.4 ± 1.2  10.0 ± 0.9  9.7 ± 0.5
Values are means ± SE of 7-9 observations in each group. Glycogen synthase (GS) fractional velocity was calculated as activity at submaximal glucose 6-phosphate concentration (0.17 mM) in percentage of maximal activity. Maximal activity was measured at saturating (8.0 mM) glucose 6-phosphate concentration. Average is average maximal activity for 22-26 observations in each group. * Significantly different from control value, P < 0.05.  dagger Significantly different from basal value, P < 0.05.

The mannitol space was larger in all Ecc-muscles compared with control (Table 3). The water content was 4.2 ± 0.5% higher in the Ecc-WG and 2.5 ± 0.5% higher in the Ecc-RG compared with control. No change was found in the Ecc-S (Table 3).

Table 3. Mannitol space and water content in calf muscles 2 days after one-legged eccentric contractions

C Ecc
Mannitol space, ml/100 g
  WG 14.0 ± 0.6  26. ± 1.5*
  RG 13.6 ± 0.8  20.9 ± 1.4*
  S 17.7 ± 0.7  20.8 ± 0.7*
Water content, ml/100 g
  WG 76.9 ± 0.2  80.0 ± 0.3*
  RG 76.1 ± 0.2  78.1 ± 0.4*
  S 78.1 ± 0.2  78.0 ± 0.2
Values are means ± SE of 22-26 observations in each group. * Significantly different from control value, P < 0.05.

DISCUSSION

The principal finding in this study is that insulin action on skeletal muscle glucose transport was impaired in fast-twitch muscle by prior eccentric contractions. The decrease was most pronounced in the WG, whereas it was less marked in the RG and no suppression was found in the S.

It has been reported that a bout of eccentric exercise transiently impairs the stimulating action of a submaximal insulin concentration on whole body glucose disposal 2 days after the bout (16), but the underlying mechanism(s) for this apparent insulin-resistant state remains obscure, involving local and/or systemic changes. The in vitro hindquarter technique allows us to measure changes of insulin action in muscle caused by prior eccentric contractions, and the results indicate that local muscle effects might at least partly be responsible for the previously observed whole body insulin resistance (16). We found the largest effect on glucose transport in the WG, in which we recently showed that muscle GLUT-4 protein content is decreased by ~65% 2 days after eccentric contractions (5). In comparison, in the RG in which the decrease in GLUT-4 protein is only ~30% (5), prior eccentric contractions impaired insulin-stimulated glucose transport less (Fig. 1). The results from these muscle types are in agreement with the view that the insulin-induced increase in muscle glucose uptake is dependent on the GLUT-4 protein content (1, 10, 15). Finally, in the S muscle, eccentric contractions had no effect on the GLUT-4 protein content (5), and the maximal insulin stimulated glucose transport was actually slightly but significantly higher in this muscle type. The latter finding was surprising, but it is possible that the more deeply located S muscle is stretched less during the stimulation than are the other more superficial calf muscles and hence contracted with a more concentric pattern, which subsequently could enhance insulin action. As judged by the previously described (5) rapid glycogen resynthesis, unchanged GLUT-4 content, and lack of signs of muscle damage in the Ecc-S after eccentric contractions, this is possible but is hard to evaluate without individual measurements of tension in the different muscles during the stimulation.

The non-insulin-stimulated glucose transport into the eccentrically damaged muscles was slightly higher compared with the control muscles in the WG and RG. This might be due to the high glucose utilization by inflammatory cells (9, 14, 26) present in the Ecc-WG and -RG (5), and also inflammatory cells have been shown to release a factor that may cause increased insulin-independent glucose metabolism in skeletal muscle (14, 26). Alternatively, if the cytosolic Ca2+ concentration is increased in damaged muscle (3), this may cause increased glucose transport (30) and might even play a role in decreasing insulin-stimulated glucose transport as well (8). However, the present study does not allow for conclusions in these respects.

Glycogen concentrations were lower in the Ecc-WG and -RG (Table 1) after perfusion with insulin at any concentration. Muscle glycogen was apparently synthesized in control muscle during perfusion with insulin because glycogen concentrations at the end of perfusions were higher than when the perfusate insulin was 0 µU/ml (Table 1). However, this was not the case in the Ecc-WG, which is in accordance with the marked decrease in insulin-stimulated glucose transport. Still, it might seem unusual that although insulin-stimulated glucose transport was decreased by 50% in the Ecc-WG compared with control, it was increased approximately sixfold compared with basal by 200 µU/ml insulin and yet absolutely no tendency to an increase in muscle glycogen from 0 to 200 µU/ml insulin was found (Table 1). This might suggest that not only is glycogen synthesis impaired by decreased glucose transport but also glycogen breakdown may be accelerated. The latter may also be part of the explanation behind the lower glycogen values in the Ecc-RG compared with control because the decrease in insulin-stimulated glucose transport, especially at low insulin concentrations, was quite small in this muscle (Fig. 1B). These findings could suggest that the subnormal muscle glycogen concentrations found for several days after eccentric contractions (5, 6, 9, 11, 20, 28) are the result of both decreased insulin action on glucose transport secondary to decreased muscle GLUT-4 protein content and increased glycogen degradation.

The extracellular space, measured by the use of [3H]mannitol, was higher in all Ecc-muscles compared with control, and also the water content was higher in the Ecc-WG and -RG compared with control. The changes in the extracellular space were pronounced with a 12 and 7 ml/g increase in the Ecc-WG and -RG compared with control muscle, whereas the total water content only was 3 and 2 ml/100 g higher in the Ecc-WG and -RG compared with control muscle, respectively. The disparate changes in mannitol space and water content indicate that the major fraction of the increase in the former after the stimulation originates from the intracellular space probably secondarily to membrane damage. Because mannitol and 3-O-methyl-D-glucose have approximately the same molecular weight (182 and 194, respectively) and are both nonpolar compounds, they likely diffuse at nearly the same rate and any increase in distribution space for mannitol should be equally large for 3-O-methyl-D-glucose. Therefore, the increased apparent distribution space for mannitol should not be a problem in the calculation of specific glucose transport. We chose to express glucose transport as specific uptake of 3-O-methyl-D-glucose into the space that is not accessible to mannitol rather than per gram of muscle because in Ecc-muscle the larger mannitol space leaves less tissue for specific glucose transport per gram of muscle. Thus expression per gram muscle would tend to decrease specific glucose transport in eccentric muscle simply because of division by a larger mass of tissue that does not participate in specific glucose transport.

The maximal activity of the enzyme glycogen synthase, which presumably reflects enzyme concentration, was on average 16% lower in the Ecc-WG, whereas it was largely unchanged in the Ecc-RG. In previous studies we found no significant decrease in the maximal activity of glycogen synthase (4, 5), which was in accordance with the results from Doyle et al. (11). However, although we found a small decrease in the maximal activity, this was much smaller than the previously reported decrease in GLUT-4 (~65%) (5) in this fiber type, suggesting that the insulin- and/or exercise-regulatable glucose transporter (GLUT-4) is especially susceptible to this type of muscle damage.

We conclude that the decrease in the muscle content of the insulin- and/or exercise-regulatable glucose transporter (GLUT-4) 2 days after eccentric contractions is accompanied by impaired insulin-stimulated muscle glucose transport. This could at least partly explain the previously described systemic insulin resistance found 2 days after eccentric exercise (16) and the sustained decreased muscle glycogen concentration after eccentric contractions. However, increased glycogen degradation may also play a significant role in muscle after eccentric contractions.

ACKNOWLEDGEMENTS

Betina Bolmgren, Nina Pfluzek, and Dorte Kesje provided skilled technical assistance.

FOOTNOTES

   The study was supported by grants from the Danish Natural Science Research Council (11-0082), the Danish National Research Foundation (504-14), Team Danmark, the Danish Sport Research Council, the Novo-Nordisk Research Council, and the Nordisk Insulin Foundation.

Address for reprint requests: S. Asp, Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, 13 Universitetsparken, DK-2100 Copenhagen Ø, Denmark (E-mail: sasp{at}aki.ku.dk).

Received 6 February 1996; accepted in final form 3 July 1996.

REFERENCES

1. Andersen, P. H., S. Lund, H. Vestergaard, S. Junker, B. B. Kahn, and O. Pedersen. Expression of the major insulin regulatable glucose transporter (GLUT-4) in skeletal muscle of non insulin-dependent diabetic patients and healthy subjects before and after insulin infusion. J. Clin. Endocrinol. Metab. 77: 27-32, 1993.
2. Ariano, M. A., R. B. Armstrong, and V. R. Edgerton. Hindlimb muscle fiber population of five mammals. J. Histochem. Cytochem. 21: 51-55, 1973.
3. Armstrong, R. B., G. L. Warren, and J. A. Warren. Mechanisms of exercise-induced muscle fibre injury. Rev. Sports Med. 12: 184-207, 1991.
4. Asp, S., J. R. Daugaard, and E. A. Richter. Eccentric exercise decreases glucose transporter GLUT-4 protein in human skeletal muscle. J. Physiol. Lond. 482: 705-712, 1995.
5. Asp, S., S. Kristiansen, and E. A. Richter. Eccentric muscle damage transiently decreases rat skeletal muscle GLUT-4 protein. J. Appl. Physiol. 79: 1338-1345, 1995.
6. Blom, P. C. S., D. L. Costill, and N. K. V<A><AC>c</AC><AC>&cjs1134;</AC></A>llestad. Exhaustive running: inappropriate as a stimulus of muscle glycogen supercompensation. Med. Sci. Sports Exercise 19: 398-403, 1987.
7. Bogardus, C., P. Thuillez, E. Ravussin, B. Vasquez, M. Narimiga, and S. Azhar. Effect of muscle glycogen depletion on in vivo insulin action in man. J. Clin. Invest. 72: 1605-1610, 1983.
8. Cartee, G. D., C. Briggs-Tung, and J. O. Holloszy. Diverse effects of calcium channel blockers on skeletal muscle glucose transport. Am. J. Physiol. 263 (Regulatory Integrative Comp. Physiol. 32): R70-R75, 1992.
9. Costill, D. L., D. D. Pascoe, J. Fink, R. A. Robergs, S. I. Barr, and D. Pearson. Impaired muscle glycogen resynthesis after eccentric exercise. J. Appl. Physiol. 69: 46-50, 1990.
10. Dela, F., A. Handberg, K. J. Mikines, J. Vinten, and H. Galbo. GLUT-4 and insulin receptor binding and kinase activity in trained human muscle. J. Physiol. Lond. 469: 615-624, 1993.
11. Doyle, J. A., W. M. Sherman, and R. L. Strauss. Effect of eccentric and concentric exercise on muscle glycogen replenishment. J. Appl. Physiol. 74: 1848-1855, 1993.
12. Dudek, R. W., G. L. Dohm, G. D. Holman, S. W. Cushman, and C. M. Wilson. Glucose transporter localization in rat skeletal muscle. Autoradiographic study using ATB-(2-3H)BMPA photolabel. FEBS Lett. 339: 205-208, 1994.
13. Etgen, G. J. J., A. R. Memon, G. A. Thompson, and J. L. Ivy. Insulin- and contraction-stimulated translocation of GTP-binding proteins and GLUT4 protein in skeletal muscle. J. Biol. Chem. 268: 20164-20169, 1993.
14. Forster, J., A. S. Morris, J. D. Shearer, B. Mastrofrancesco, K. C. Inman, R. G. Lawler, W. Bowen, and M. D. Caldwell. Glucose uptake and flux through phosphofructokinase in wounded rat skeletal muscle. Am. J. Physiol. 256 (Endocrinol. Metab. 19): E788-E797, 1989.
15. Henriksen, E. J., R. E. Bourey, K. J. Rodnick, L. Koranyi, M. A. Permutt, and J. O. Holloszy. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. Am. J. Physiol. 259 (Endocrinol. Metab. 22): E593-E598, 1990.
16. Kirwan, J. P., J. P. Hickner, K. E. Yarasheski, W. M. Kohrt, B. V. Wiethop, and J. O. Holloszy. Eccentric exercise induces transient insulin resistance in healthy individuals. J. Appl. Physiol. 72: 2197-2203, 1992.
17. Kong, X., J. Manchester, S. Salmons, and J. C. Lawrence, Jr. Glucose transporters in single skeletal muscle fibers. J. Biol. Chem. 269: 12963-12967, 1994.
18. Lowry, O. H., and J. V. Passonneau. A Flexible System of Enzymatic Analysis. New York: Academic, 1972.
19. Mikines, K., B. Sonne, P. Farrell, B. Tronier, and H. Galbo. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am. J. Physiol. 254 (Endocrinol. Metab. 17): E248-E259, 1988.
20. O'Reilly, K. P., M. J. Warhol, R. A. Fielding, W. R. Frontera, C. N. Meredith, and W. J. Evans. Eccentric exercise-induced muscle damage impairs muscle glycogen repletion. J. Appl. Physiol. 63: 252-256, 1987.
21. Richter, E. A., L. P. Garetto, M. N. Goodman, and N. B. Ruderman. Muscle glucose metabolism following exercise in the rat. J. Clin. Invest. 69: 785-793, 1982.
22. Richter, E. A., K. J. Mikines, H. Galbo, and B. Kiens. Effect of exercise on insulin action in human skeletal muscle. J. Appl. Physiol. 66: 876-885, 1989.
23. Richter, E. A., T. Ploug, and H. Galbo. Increased muscle glucose uptake after exercise. Diabetes 34: 1041-1048, 1985.
24. Richter, E. A., N. B. Ruderman, H. Gavras, E. R. Belur, and H. Galbo. Muscle glycogenolysis during exercise: dual control by epinephrine and contractions. Am. J. Physiol. 242 (Endocrinol. Metab. 5): E25-E32, 1982.
25. Ruderman, N. B., C. R. S. Houghton, and R. Hems. Evaluation of the isolated perfused rat hindquarter for the study of muscle metabolism. Biochem. J. 124: 639-651, 1971.
26. Shearer, J. D., J. F. Amaral, and M. D. Caldwell. Glucose metabolism of injured skeletal muscle: the contribution of inflammatory cells. Circ. Shock 25: 131-138, 1988.
27. Thomas, J. A., K. K. Schlender, and J. Larner. A rapid filter paper assay for UDPglucose-glycogen glucosyl-transferase, including an improved biosynthesis of UDP-14C-glucose. Anal. Biochem. 25: 486-499, 1968.
28. Widrick, J. J., D. L. Costill, G. K. McConell, D. E. Anderson, D. R. Pearson, and J. J. Zachwieja. Time course of glycogen accumulation after eccentric exercise. J. Appl. Physiol. 72: 1999-2004, 1992.
29. Wilson, C. M., and S. W. Cushman. Insulin stimulation of glucose transport activity in rat skeletal muscle: increase in cell surface GLUT-4 assessed by photolabelling. Biochem. J. 299: 755-759, 1994.
30. Youn, J. H., E. A. Gulve, and J. O. Holloszy. Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contraction. Am. J. Physiol. 260 (Cell Physiol. 29): C555-C561, 1991.
0161-7567/96 $5.00 Copyright © 1996 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Am. Coll. Nutr.Home page
W. J. Evans
Protein Nutrition, Exercise and Aging
J. Am. Coll. Nutr., December 1, 2004; 23(suppl_6): 601S - 609S.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. M. Hernandez, M. J. Fedele, and P. A. Farrell
Time course evaluation of protein synthesis and glucose uptake after acute resistance exercise in rats
J Appl Physiol, March 1, 2000; 88(3): 1142 - 1149.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
L. F. del Aguila, K. P. Claffey, and J. P. Kirwan
TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells
Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E849 - E855.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
S. Asp, A. Watkinson, N. D. Oakes, and E. W. Kraegen
Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat
J Appl Physiol, April 1, 1997; 82(4): 1327 - 1332.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Asp, S.
Right arrow Articles by Richter, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Asp, S.
Right arrow Articles by Richter, E. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online