Eccentric muscle damage transiently decreases rat skeletal muscle GLUT-4 protein

1995 ◽  
Vol 79 (4) ◽  
pp. 1338-1345 ◽  
Author(s):  
S. Asp ◽  
S. Kristiansen ◽  
E. A. Richter
Keyword(s):  
Protein Content ◽  
Muscle Damage ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Eccentric Contractions ◽  
Phagocytic Cells ◽  
Glut 4 ◽  
Eccentric Muscle Damage ◽  
Gastrocnemius Muscles ◽  
Calf Muscles

The effects of concentric and muscle-damaging eccentric contractions on muscle glucose transporter GLUT-4 content were studied in rat muscles. Rats were anesthetized, the calf muscles on one side were stimulated electrically for concentric or eccentric contractions, and bilateral calf muscles were obtained in the postexercise period. Inflammatory and phagocytic cells accumulated in the eccentric white and red gastrocnemius muscles, whereas there were only discrete changes in the eccentric soleus. Glycogen was depleted to the same extent in the white and red gastrocnemius muscles after both types of stimulation, and it remained decreased > 2 days in eccentric muscles. The total GLUT-4 protein content was decreased in the eccentric white and red gastrocnemius muscles 1 and 2 days after the eccentric stimulation, whereas the maximal activity of glycogen synthase was unaffected at these time points. In conclusion, our one-legged stimulation model caused eccentric muscle damage in the white and red gastrocnemius, whereas only minor damage was observed in the soleus muscle. In damaged muscle, muscle glycogen and GLUT-4 protein content were decreased for > 2 days. These findings may suggest (but do not prove) that decreased muscle GLUT-4 protein is involved in the delayed glycogen resynthesis after eccentric exercise.

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

1996 ◽  
Vol 81 (5) ◽  
pp. 1924-1928 ◽  
Author(s):  
Sven Asp ◽  
Erik A. Richter
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Eccentric Contractions ◽  
Gastrocnemius Muscles ◽  
Muscle Glucose Transport ◽  
And Control ◽  
Glycogen Synthase Activity ◽  
Calf Muscles

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). 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.

Eccentric contractions decrease glucose transporter transcription rate, mRNA, and protein in skeletal muscle

1997 ◽  
Vol 272 (5) ◽  
pp. C1734-C1738 ◽  
Author(s):  
S. Kristiansen ◽  
J. Jones ◽  
A. Handberg ◽  
G. L. Dohm ◽  
E. A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Glucose Transport ◽  
Gastrocnemius Muscle ◽  
Glucose Transporter ◽  
Mrna Level ◽  
Eccentric Contractions ◽  
Transcription Rate ◽  
Rat Skeletal Muscle ◽  
Glut 4

We have recently shown that eccentric contractions (ECs; forced lengthening of active muscle) elicit a delayed decrease in glucose transporter (GLUT-4) protein content in rat skeletal muscle and a decrease in subsequent contraction-stimulated glucose transport. Here, we investigate whether this decrease in total GLUT-4 protein after prior ECs is due to changes in GLUT-4 gene transcription rate and GLUT-4 mRNA level. Furthermore, the effect of prior ECs on sarcolemmal GLUT-4 protein content in plasma membrane (PM) vesicles isolated from contraction-stimulated muscle was determined. Rat gastrocnemius muscle was electrically stimulated for ECs, and the contralateral muscle served, as unstimulated control (UC). Two days later, the total GLUT-4 protein content was decreased by 50% (P < 0.05) and 32% (P < 0.05) in the white and red gastrocnemius muscle, respectively. Furthermore, the GLUT-4 mRNA concentration was decreased by 41% (P < 0.05) in both the white and red gastrocnemius muscle. Moreover, the GLUT-4 transcription rate, determined by nuclear run-on analysis, was decreased by 75% (P < 0.05) in mixed EC gastrocnemius muscle compared with UC muscle. PM vesicles were isolated from EC and UC muscle after 15 min of isometric contractions. The PM GLUT-4 protein content was reduced by 51% (P < 0.05) in EC muscle compared with UC muscle. In conclusion, 2 days after ECs, the GLUT-4 transcription rate, GLUT-4 mRNA, and GLUT-4 protein content were decreased in rat skeletal muscle. Moreover, the PM GLUT-4 protein content in contraction-stimulated muscle was decreased. We suggest that eccentric muscle contractions decrease muscle GLUT-4 transcription rate, resulting in a lower GLUT-4 protein content, which in turn decreases the number of GLUT-4 transporters translocated to the sarcolemma, ultimately leading to decreased contraction-induced muscle glucose transport.

Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Hexokinase Ii ◽  
Epinephrine Infusion ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

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.

Effect of chronic electrical stimulation on GLUT-4 protein content in fast-twitch muscle

1993 ◽  
Vol 264 (4) ◽  
pp. R816-R819 ◽  
Author(s):  
G. J. Etgen ◽  
R. P. Farrar ◽  
J. L. Ivy
Keyword(s):  
Electrical Stimulation ◽  
Protein Content ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Low Frequency ◽  
Neuromuscular Activity ◽  
Glut 4 ◽  
Fast Twitch Muscle ◽  
Chronic Electrical Stimulation ◽  
Fast Twitch

Insulin- and contraction-stimulated skeletal muscle glucose transport is governed largely by the GLUT-4 isoform of the glucose transporter. Recently, it has been demonstrated that denervated muscle has decreased GLUT-4 protein content, suggesting that regulation of GLUT-4 protein is related to neuromuscular activity. However, until now the effects of the opposite situation, enhanced neuromuscular activity, could only be speculated on from exercise training studies. In the present investigation the effect of chronic low-frequency electrical stimulation (10 Hz, 8 h/day) on GLUT-4 protein content and citrate synthase activity was determined in the predominantly fast-twitch plantaris. Chronic electrical stimulation enhanced GLUT-4 protein content and citrate synthase activity in the muscles stimulated for 10-20 days. Electrical stimulation lasting 30-40 days resulted in no further enhancement of GLUT-4 protein content while citrate synthase activity continued to increase. Further prolongation of electrical stimulation (60-90 days) resulted in a plateauing of citrate synthase activity. The results suggest that increased neuromuscular activity can act independently of systemic changes to increase total GLUT-4 protein content. They also suggest that both GLUT-4 protein content and citrate synthase activity are positively related to increased neuromuscular activity but that their rates of increase differ substantially.

Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats

2001 ◽  
Vol 281 (5) ◽  
pp. E1101-E1109 ◽  
Author(s):  
María Agote ◽  
Luis Goya ◽  
Sonia Ramos ◽  
Carmen Alvarez ◽  
M. Lucía Gavete ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Subcellular Fractionation ◽  
Phosphatidylinositol 3 Kinase ◽  
Glut 4 ◽  
Gastrocnemius Muscles ◽  
Glucose Transporter Proteins ◽  
And Control

Undernutrition in rats impairs secretion of insulin but maintains glucose normotolerance, because muscle tissue presents an increased insulin-induced glucose uptake. We studied glucose transporters in gastrocnemius muscles from food-restricted and control anesthetized rats under basal and euglycemic hyperinsulinemic conditions. Muscle membranes were prepared by subcellular fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food-restricted rats, respectively. Muscle insulin receptor was increased, but phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by insulin was lower in undernourished rats, whereas insulin receptor substrate-1 content remained unaltered. The main glucose transporter in the muscle, GLUT-4, was severely reduced albeit more efficiently translocated in response to insulin in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal muscle, were found increased in food-deprived rats. The rise in these minor glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably insufficient to account for the insulin-induced increase in the uptake of glucose in undernourished rats, thereby suggesting possible changes in other steps required for glucose metabolism.

Decreased muscle GLUT-4 and contraction-induced glucose transport after eccentric contractions

1996 ◽  
Vol 271 (2) ◽  
pp. R477-R482 ◽  
Author(s):  
S. Kristiansen ◽  
S. Asp ◽  
E. A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Glucose Transport ◽  
Eccentric Exercise ◽  
Muscle Performance ◽  
Eccentric Contractions ◽  
Tension Development ◽  
Glut 1 ◽  
Glut 4 ◽  
Muscle Glucose Transport

Eccentric exercise causes muscle damage and decreased muscle glycogen and glucose transporter isoform (GLUT-4) protein content. We investigated whether the contraction-induced increase in skeletal muscle glucose transport and muscle performance is affected by prior eccentric contractions. The calf muscles from rats were stimulated for eccentric (EC) or concentric (CC) contractions or were passively stretched (ST). Muscles from unstimulated control (CT) rats were also studied. Two days later, all rats had their isolated hindlimbs perfused either at rest or during 15 min of isometric muscle contractions. EC rats had a significantly lower total GLUT-4 protein content in the white gastrocnemius (GW) muscle (55%) and red gastrocnemius (GR) muscle (34%) compared with muscle from the CT, ST, and CC rats. In contrast, GLUT-1 protein content was approximately twofold higher in the GW muscle in EC rats than in CT rats. In the GW and GR muscle, prior eccentric exercise decreased contraction-induced stimulation of glucose transport compared with CT, ST, and CC rats despite no difference in tension development and oxygen uptake among the groups. There was no change in total GLUT-4 content and glucose transport in the soleus (S) muscle among the four group. It is concluded that the GLUT-4 and GLUT-1 protein contents in fast-twitch muscle are decreased and increased, respectively, 2 days after eccentric contractions. The functional consequence of these changes appears to be decreased contraction-induced increase in skeletal muscle glucose transport.

Seven days of exercise increase GLUT-4 protein content in human skeletal muscle

1995 ◽  
Vol 79 (6) ◽  
pp. 1936-1938 ◽  
Author(s):  
J. A. Houmard ◽  
M. S. Hickey ◽  
G. L. Tyndall ◽  
K. E. Gavigan ◽  
G. L. Dohm
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Content ◽  
Human Skeletal Muscle ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Cycle Ergometer ◽  
Maximal Heart Rate ◽  
Short Term ◽  
Glut 4

Insulin-responsive glucose transporter (GLUT-4) content increases by 1.8-fold in skeletal muscle with 14 wk of exercise training [Houmard et al. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E896-E901, 1993]. The purpose of this study was to determine whether more short-term training (7 days) increases GLUT-4 protein content in human skeletal muscle. Seven sedentary men [25.0 +/- 1.1 (SE) yr, 44.1 +/- 2.2 ml.kg-1.min-1 maximal O2 uptake, 14.9 +/- 2.1% body fat] were examined before and after 7 days of cycle ergometer training (1 h/day, 76 +/- 2% maximal heart rate). Needle biopsy samples from the vastus lateralis were used to determine GLUT-4 protein content. Muscle GLUT-4 increased (P < 0.05) by an average of 2.8 +/- 0.5-fold with 7 days of training. GLUT-4 content in skeletal muscle thus increases substantially with short-term exercise training.

Skeletal muscle glucose transporter (GLUT-4) protein is decreased in lactating goats

1997 ◽  
Vol 65 (2) ◽  
pp. 257-265 ◽  
Author(s):  
M. Balage ◽  
J. F. Hocquette ◽  
B. Graulet ◽  
P. Ferre ◽  
J. Grizard
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Glut 4 ◽  
Lactating Goats ◽  
Insulin Responsiveness ◽  
Triton X

AbstractLactation in goats is associated with an insulin resistance manifested by an impairment of the ability of insulin maximally to stimulate skeletal muscle glucose utilization. The mechanism responsible for this modification is unknown. Therefore an investigation was made of the insulin-sensitive glucose transporter (GLUT-4) in three skeletal muscles from six lactating (peak of lactation) and six non-lactating goats. GLUT-4 protein content was assessed in crude membrane preparations and Triton X-100 extracts by Western-blot analysis. Lactation resulted in a decrease in GLUT-4 protein content. This decrease was more pronounced in oxidoglycolytic muscles (proportionately -0·40 to -0·60 in m. tensor fasciae latae and longissimus dorsi) than in oxidative muscles (-0·20 in masseter). Down-regulation of the insulin-sensitive glucose transporter (GLUT-4) expression in skeletal muscles from lactating goats may be responsible for the decrease in insulin responsiveness of glucose utilization previously observed in vivo.

Role of the calcium-calpain pathway in cytoskeletal damage after eccentric contractions

2008 ◽  
Vol 105 (1) ◽  
pp. 352-357 ◽  
Author(s):  
Bao-Ting Zhang ◽  
Simon S. Yeung ◽  
David G. Allen ◽  
Ling Qin ◽  
Ella W. Yeung
Keyword(s):  
Muscle Damage ◽  
Muscle Force ◽  
Cytoskeletal Proteins ◽  
Eccentric Contractions ◽  
Membrane Disruption ◽  
Control Group ◽  
Calpain Inhibitor ◽  
Dependent Manner ◽  
Eccentric Muscle Damage

The mechanism(s) underlying eccentric damage to skeletal muscle cytoskeleton remain unclear. We examined the role of Ca2+ influx and subsequent calpain activation in eccentric damage to cytoskeletal proteins. Eccentric muscle damage was induced by stretching isolated mouse muscles by 20% of the optimal length in a series of 10 tetani. Muscle force and immunostaining of the cytoskeletal proteins desmin, dystrophin, and titin were measured at 5, 15, 30, and 60 min after eccentric contractions and compared with the control group that was subjected to 10 isometric contractions. A Ca2+-free solution and leupeptin (100 μM), a calpain inhibitor, were applied to explore the role of Ca2+ and calpain, respectively, in eccentric muscle damage. After eccentric contractions, decreases in desmin and dystrophin immunostaining were apparent after 5 min that accelerated over the next 60 min. Increased titin immunostaining, thought to indicate damage to titin, was evident 10 min after stretch, and fibronectin entry, indicating membrane disruption, was evident 20 min after stretch. These markers of damage also increased in a time-dependent manner. Muscle force was reduced immediately after stretch and continued to fall, reaching 56 ± 2% after 60 min. Reducing extracellular calcium to zero or applying leupeptin minimized the changes in immunostaining of cytoskeletal proteins, reduced membrane disruption, and improved the tetanic force. These results suggest that the cytoskeletal damage and membrane disruption were mediated primarily by increased Ca2+ influx into muscle cells and subsequent activation of calpain.

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