Glucose transporters and maximal transport are increased in endurance-trained rat soleus

1992 ◽  
Vol 73 (2) ◽  
pp. 486-492 ◽  
Author(s):  
C. A. Slentz ◽  
E. A. Gulve ◽  
K. J. Rodnick ◽  
E. J. Henriksen ◽  
J. H. Youn ◽  
...  
Keyword(s):  
Training Program ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Protein Concentration ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Contractile Activity ◽  
Treadmill Running ◽  
Female Rats ◽  
Transport Activity

Voluntary wheel running induces an increase in the concentration of the regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425–1429, 1990). Wheel running also causes hypertrophy of the soleus in rats. This study was undertaken to ascertain whether endurance training that induces enzymatic adaptations but no hypertrophy results in an increase in the concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it does, to determine whether there is a concomitant increase in maximal glucose transport activity. Female rats were trained by treadmill running at 25 m/min up a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy. Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training. In a second set of experiments, we examined whether a swim-training program increases glucose transport activity in the soleus in the presence of a maximally effective concentration of insulin. The swimming program induced a 44% increase in immunoreactive GLUT4 protein concentration. Glucose transport activity maximally stimulated with insulin was 62% greater in soleus muscle of the swimmers than in untrained controls. Training did not alter the basal rate of 2-deoxyglucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats

1994 ◽  
Vol 76 (5) ◽  
pp. 1862-1867 ◽  
Author(s):  
E. J. Henriksen ◽  
A. E. Halseth
Keyword(s):  
Glucose Transport ◽  
Soleus Muscle ◽  
Protein Level ◽  
Wheel Running ◽  
Glycogen Synthase ◽  
Female Rats ◽  
Total Protein Content ◽  
Transport Activity ◽  
Glycogen Concentration ◽  
Glut 4

Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%; P < 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2–4 (+24–32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity (+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25–28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21–42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to -41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However, this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.

Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression

1993 ◽  
Vol 264 (1) ◽  
pp. C146-C150 ◽  
Author(s):  
J. M. Ren ◽  
C. F. Semenkovich ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Oxidative Enzymes ◽  
Mitochondrial Enzymes ◽  
Striated Muscles ◽  
Transport Activity ◽  
Glut 4 ◽  
Depletion Effect

Feeding rats beta-guanidinopropionic acid (beta-GPA), a creatine analogue, results in depletion of creatine and phosphocreatine and induces increases in mitochondrial oxidative enzymes and hexokinase in skeletal muscle. Comparisons of different muscle types and studies of the adaptation to exercise suggest that 1) the levels of the insulin-responsive glucose transporter (GLUT-4), mitochondrial oxidative enzymes, and hexokinase may be coregulated and 2) GLUT-4 content can determine maximal glucose transport activity in muscle. To further evaluate these possibilities, we examined the effects of feeding rats 1% beta-GPA in their diet for 6 wk on muscle GLUT-4 expression and glucose transport activity. beta-GPA feeding induced 40-50% increases in cytochrome c concentration, citrate synthase activity, and hexokinase activity in plantaris muscle. GLUT-4 protein concentration was increased approximately 50% in plantaris and epitrochlearis muscles, while GLUT-4 mRNA was increased approximately 40% in plantaris muscles of beta-GPA-fed rats. Glucose transport activity maximally stimulated by insulin was increased in parallel with GLUT-4 protein concentration in the epitrochlearis. These results provide evidence that chronic creatine depletion increases GLUT-4 expression by pretranslational mechanisms. They support the hypothesis that the levels of mitochondrial enzymes, hexokinase, and GLUT-4 protein are coregulated in striated muscles. They also support the concept that the GLUT-4 content of a muscle determines its maximal glucose transport activity when the signaling pathways for glucose transport activation are intact.

Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats

1993 ◽  
Vol 264 (3) ◽  
pp. E319-E327 ◽  
Author(s):  
E. A. Gulve ◽  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
J. H. Youn ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Transport Activity ◽  
Glut 4 ◽  
Flexor Digitorum Brevis ◽  
Old Rats ◽  
Growth And Aging ◽  
Flexor Digitorum

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose transporter protein content and glucose transport capacity in rat skeletal muscles

1990 ◽  
Vol 259 (4) ◽  
pp. E593-E598 ◽  
Author(s):  
E. J. Henriksen ◽  
R. E. Bourey ◽  
K. J. Rodnick ◽  
L. Koranyi ◽  
M. A. Permutt ◽  
...  
Keyword(s):  
Protein Content ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Fiber Type ◽  
Linear Regression Analysis ◽  
Type I ◽  
Fiber Types ◽  
Transport Activity ◽  
Glut 4

The relationships among fiber type, glucose transporter (GLUT-4) protein content, and glucose transport activity stimulated maximally with insulin and/or contractile activity were studied by use of the rat epitrochlearis (15% type I-20% type II2a-65% type IIb), soleus (84-16-0%), extensor digitorum longus (EDL, 3-57-40%), and flexor digitorum brevis (FDB, 7-92-1%) muscles. Insulin-stimulated 2-deoxy-D-glucose (2-DG) uptake was greatest in the soleus, followed (in order) by the FDB, EDL, and epitrochlearis. On the other hand, contractile activity induced the greatest increase in 2-DG uptake in the FDB, followed by the EDL, soleus, and epitrochlearis. The effects of insulin and contractile activity on 2-DG uptake were additive in all the muscle preparations, with the relative rates being FDB greater than soleus greater than EDL greater than epitrochlearis. Quantitation of the GLUT-4 protein content with the antiserum R820 showed the following pattern: FDB greater than soleus greater than EDL greater than epitrochlearis. Linear regression analysis showed that whereas a relatively low and nonsignificant correlation existed between GLUT-4 protein content and 2-DG uptake stimulated by insulin alone, significant correlations existed between GLUT-4 protein content and 2-DG uptake stimulated either by contractions alone (r = 0.950) or by insulin and contractions in combination (r = 0.992). These results suggest that the differences in maximally stimulated glucose transport activity among the three fiber types may be related to differences in their content of GLUT-4 protein.

Capillary tortuosity in rat soleus muscle is not affected by endurance training

1989 ◽  
Vol 256 (4) ◽  
pp. H1110-H1116 ◽  
Author(s):  
D. C. Poole ◽  
O. Mathieu-Costello ◽  
J. B. West
Keyword(s):  
Exercise Training ◽  
Citrate Synthase ◽  
Metabolic Response ◽  
Oxidative Capacity ◽  
Treadmill Running ◽  
Female Rats ◽  
Capillary Length ◽  
Direct Function ◽  
Musculus Soleus ◽  
Muscle Changes

The total capillary length available for blood-tissue transfer is determined by the number and orientation of the capillaries. Therefore, whether capillary tortuosity changes with exercise training has important implications for peripheral gas exchange. To determine the effects of exercise training on capillary orientation and capillary length per volume of muscle fiber [Jv(c,f)] female rats were trained by treadmill running (30 m/min, up to 60 min/day, 5 days/wk) for 4 wk. Muscles from control and trained rats were perfusion fixed at sarcomere lengths (l) ranging from 1.59 to 2.15 microns, and morphometric techniques were used to estimate capillary orientation and Jv(c,f). Training increased (P less than 0.05) musculus soleus oxidative capacity 35% [as estimated from citrate synthase activity: 24.7 +/- 1.4 to 34.7 +/- 1.0 (SE) mumol.g-1.min-1], capillary-to-fiber ratio 30% (2.17 +/- 0.06 to 2.83 +/- 0.05), and Jv(c,f) 32% (1,886 +/- 73 to 2,496 +/- 180 mm-2). Capillary tortuosity (as determined from comparisons of transverse and longitudinal sections) was a direct function of l in control and trained rats and contributed 17-73% of capillary length above that estimated from capillary counts on transverse sections. We conclude that capillary tortuosity in m. soleus is unchanged by training. Therefore, Jv(c,f) increases as a consequence of increased capillary number. M. soleus citrate synthase activity is best correlated with Jv(c,f) and not with capillary counts on transverse sections. We hypothesize that training-induced muscle changes of capillary geometry improve O2 delivery to skeletal muscle and may therefore alter the metabolic response (e.g., lactate accumulation) to exercise after training.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of glucose transport in glycogen supercompensation in reweighted rat skeletal muscle

1996 ◽  
Vol 80 (5) ◽  
pp. 1540-1546 ◽  
Author(s):  
E. J. Henriksen ◽  
C. S. Stump ◽  
T. H. Trinh ◽  
S. D. Beaty
Keyword(s):  
Glucose Transport ◽  
Citrate Synthase ◽  
Specific Activity ◽  
Glycogen Synthase ◽  
Average Rate ◽  
Weight Bearing ◽  
Hindlimb Suspension ◽  
Transport Activity ◽  
Glut 4 ◽  
Insulin Dependent

Hindlimb weight bearing after a 3-day period of hindlimb suspension (reweighting) of juvenile rats results in a marked transient elevation in soleus glycogen concentration that cannot be explained on the basis of the activities of glycogen synthase and phosphorylase. We have hypothesized that enhanced glucose transport activity could underlie this response. We directly tested this hypothesis by assessing the response of insulin-dependent and insulin-independent glucose transport activity (in vitro 2-[1,2-3H]deoxy-D-glucose uptake) as well as glucose transporter (GLUT-4) protein levels during a 48-h reweighting period. After a net glycogen loss (from 29 +/- 2 to 16 +/- 1 nmol/mg muscle; P < 0.05) during the first 2 h of reweighting, glycogen accumulated at an average rate of 1.4 nmol.mg-1.h-1 up to 18 h, reaching an apex of 38 +/- 1 nmol/mg. During this same reweighting period, insulin-independent, but not insulin-dependent, glucose transport activity was significantly enhanced (P < 0.05 vs. weight-bearing control values) and was associated with an elevated level of GLUT-4 protein and the specific activity of total hexokinase. The specific activity of citrate synthase was also increased. By 24 h of reweighting, although insulin-independent glucose transport activity and GLUT-4 protein remained elevated, glycogen accumulation had ceased, likely due to enhanced phosphorylase activity at this time point. These results are consistent with the interpretation that the glycogen supercompensation seen during reweighting of the rat soleus may be regulated in part by an enhanced glucose flux arising from an increase in insulin-independent glucose transport activity and hexokinase activity.

Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction

1992 ◽  
Vol 263 (6) ◽  
pp. E1157-E1163 ◽  
Author(s):  
M. T. Falduto ◽  
A. P. Young ◽  
R. C. Hickson
Keyword(s):  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Muscle Atrophy ◽  
Contractile Activity ◽  
Hormone Treatment ◽  
Quadriceps Muscle ◽  
Treadmill Running ◽  
Female Rats ◽  
Glucocorticoid Treatment ◽  
Fast Twitch

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle

1990 ◽  
Vol 258 (4) ◽  
pp. C648-C653 ◽  
Author(s):  
E. J. Henriksen ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Cytochalasin B ◽  
Contractile Activity ◽  
Transport Activity ◽  
Rat Skeletal Muscle ◽  
Phenylarsine Oxide ◽  
Muscle Glucose Transport ◽  
Glucose Analogue ◽  
Stimulation Of

The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (greater than 5 microM) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3-MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (greater than or equal to 20 microM) prevented approximately 80% of the increase in 3-MG transport caused by insulin, it resulted in only a approximately 50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 microM) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself.

Effects of exercise training on glucose transport and cell surface GLUT-4 in isolated rat epitrochlearis muscle

1997 ◽  
Vol 272 (2) ◽  
pp. E320-E325 ◽  
Author(s):  
T. H. Reynolds ◽  
J. T. Brozinick ◽  
M. A. Rogers ◽  
S. W. Cushman
Keyword(s):  
Exercise Training ◽  
Cell Surface ◽  
Glucose Transport ◽  
Muscle Glycogen ◽  
Citrate Synthase ◽  
Transport Activity ◽  
Glut 4 ◽  
Isolated Rat

The effects of exercise training on maximal glucose transport activity and cell surface GLUT-4 were examined in rat epitrochlearis muscle. Five days of swim training (2 x 3 h/day) produce a significant increase in citrate synthase activity (24.5 +/- 0.6 vs. 20.1 +/- 0.7 micromol x min(-1) x g(-1)), GLUT-4 content (22.9 +/- 0.8 vs. 17.4 +/- 0.4% GLUT-4 standard), and glycogen levels (54.3 +/- 9.4 vs. 28.6 +/- 9.4 micromol/g). Maximally, insulin-stimulated glucose transport activity and cell surface GLUT-4 are increased by 55 (1.50 +/- 0.11 vs. 0.97 +/- 0.10 micromol x ml(-1) x 20 min(-1)) and 48% [12.0 +/- 0.8 vs. 8.1 +/- 0.9 disintegrations x min(-1) (dpm) x mg(-1)], respectively, in exercise-trained epitrochlearis muscles. In contrast, hypoxia-stimulated glucose transport activity and cell surface GLUT-4 are reduced by 38 (0.78 +/- 0.08 vs.1.25 +/- 0.14 micromol x ml(-1) x 20 min(-1)) and 40% (5.7 +/- 0.9 vs. 9.4 +/- 1.2 dpm/mg), respectively, in exercise-trained epitrochlearis muscles. These results demonstrate that changes in insulin- and hypoxia-stimulated glucose transport activity after exercise training are fully accounted for by the appearance of cell surface GLUT-4 and support the concept of two intracellular pools of GLUT-4. Finally, we propose that high levels of muscle glycogen with exercise training may contribute to the decrease in hypoxia-stimulated glucose transport activity.

Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice

1993 ◽  
Vol 74 (1) ◽  
pp. 388-395 ◽  
Author(s):  
B. MacNeil ◽  
L. Hoffman-Goetz
Keyword(s):  
Citrate Synthase ◽  
Wheel Running ◽  
In Vitro Cytotoxicity ◽  
Treadmill Running ◽  
Pulmonary Vasculature ◽  
Control Group ◽  
Natural Immunity ◽  
Chronic Exercise

This study investigated the influence of 9 wk of chronic exercise on natural cytotoxicity in male C3H mice. Both in vivo cytotoxicity (pulmonary vasculature) and in vitro cytotoxicity (spleen) were determined for voluntary (wheel running; n = 30) and forced (treadmill running, 15 m/min, 30 min/day; n = 30) exercise protocols. A sedentary control group (n = 30) and a treadmill control group (5 m/min, 5 min/day; n = 30) were also included. After 9 wk of chronic exercise, submaximal exercise O2 uptake was reduced in the wheel-running group relative to that in sedentary or treadmill-trained mice. Maximal citrate synthase activity of soleus muscle was higher in treadmill-trained group compared with that in sedentary or wheel-running mice. Chronic exercise consistently reduced percent retention of CIRAS 3 tumor cells in the lungs of treadmill- (15.3 +/- 1.4) and wheel- (17.9 +/- 1.4) trained mice below that of sedentary (29.5 +/- 2.7) and treadmill control (25.8 +/- 1.8) groups (P < 0.001). Injection of anti-asialo GM1 (ASGM1) antibody increased tumor cell retention in the lungs for all groups but did not alter the differences between activity conditions. In vitro cytotoxicity was enhanced in treadmill- and wheel-trained mice relative to that in sedentary controls but was not elevated in the treadmill control group. Anti-ASGM1 injection eliminated in vitro cytotoxicity for all groups. Chronic exercise slightly increased the frequency of ASGM1-positive splenocytes in treadmill-trained mice only. These results indicate that chronic exercise enhances natural cytotoxic mechanisms in vivo and in vitro and that this enhancement is present for both forced and voluntary exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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