Exercise-induced translocation of skeletal muscle glucose transporters

1991 ◽  
Vol 261 (6) ◽  
pp. E795-E799 ◽  
Author(s):  
L. J. Goodyear ◽  
M. F. Hirshman ◽  
E. S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Glucose Transporters ◽  
Transporter Protein ◽  
Glut 4 ◽  
Microsomal Membranes ◽  
Exercise Induced ◽  
Muscle Contractile

Skeletal muscle contractile activity results in increased rates of glucose transport that are associated with an increase in the number and activity of plasma membrane glucose transporters. In the current study it was determined whether exercise causes a translocation of glucose transporters from an intracellular pool to the plasma membrane and whether exercise and insulin stimulate the same glucose transporter protein. Plasma membrane glucose transporter number, measured by cytochalasin B binding, increased from 10.1 +/- 0.73 to 15.0 +/- 1.4 pmol/mg protein (P less than 0.01) in muscle of exercised rats, whereas microsomal membrane transporters decreased significantly from 6.0 +/- 0.7 to 4.2 +/- 0.4 pmol/mg protein (P less than 0.05). Western blot analysis using the monoclonal antibody mAb 1F8 (specific for GLUT-4) demonstrated a 45% increase in plasma membrane GLUT-4 from exercised skeletal muscle compared with controls, whereas microsomal membranes from the exercised muscle had a concomitant 25% decrease in GLUT-4 protein. These data suggest that exercise recruits transporters to the plasma membrane from an intracellular microsomal pool, similar to the translocation of transporters that occurs with insulin stimulation. Furthermore, both exercise and insulin stimulate the translocation of GLUT-4 in skeletal muscle, while GLUT-1 is not altered.

Insulin induces translocation of GLUT-4 glucose transporters in human skeletal muscle

1995 ◽  
Vol 268 (4) ◽  
pp. E613-E622 ◽  
Author(s):  
A. Guma ◽  
J. R. Zierath ◽  
H. Wallberg-Henriksson ◽  
A. Klip
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Glucose Transporters ◽  
Membrane Markers ◽  
Glut 4 ◽  
Muscle Biopsies

Understanding the molecular mechanisms involved in the regulation of glucose transport into human muscle is necessary to unravel possible defects in glucose uptake associated with insulin resistance in humans. Here we report a strategy to subfractionate human skeletal muscle biopsies (0.5 g) removed from vastus lateralis during a euglycemic insulinemic clamp procedure. A sucrose gradient separated total membranes into five fractions. Fraction 25 (25% sucrose) contained the plasma membrane markers alpha 1- and alpha 2-subunits of the Na(+)-K(+)-adenosinetriphosphatase and the GLUT-5 hexose transporter, recently immunolocalized to the cell surface of human skeletal muscle. The dihydropyridine receptor, a transverse tubule marker, was present exclusively in this fraction. The GLUT-4 glucose transporter was more concentrated in fraction 27.5 (27.5% sucrose) and largely diminished in plasma membrane markers. Open skeletal muscle biopsies were removed before and 30 min after clamping insulin to 550 pM. This increased GLUT-4 protein by 1.61-fold in fraction 25 and lowered it by 50% in fraction 27.5. Thus physiological concentrations of insulin induce translocation of glucose transporters from an internal membrane pool to surface membranes in human skeletal muscle.

Expression and cellular localization of glucose transporters (GLUT1, GLUT3, GLUT4) during differentiation of myogenic cells isolated from rat foetuses

1994 ◽  
Vol 107 (3) ◽  
pp. 487-496 ◽  
Author(s):  
I. Guillet-Deniau ◽  
A. Leturque ◽  
J. Girard
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Cell Fusion ◽  
Cellular Localization ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Short Exposure ◽  
Myoblast Differentiation ◽  
Igf I

Skeletal muscle regeneration is mediated by the proliferation of myoblasts from stem cells located beneath the basal lamina of myofibres, the muscle satellite cells. They are functionally indistinguishable from embryonic myoblasts. The myogenic process includes the fusion of myoblasts into multinucleated myotubes, the biosynthesis of proteins specific for skeletal muscle and proteins that regulates glucose metabolism, the glucose transporters. We find that three isoforms of glucose transporter are expressed during foetal myoblast differentiation: GLUT1, GLUT3 and GLUT4; their relative expression being dependent upon the stage of differentiation of the cells. GLUT1 mRNA and protein were abundant only in myoblasts from 19-day-old rat foetuses or from adult muscles. GLUT3 mRNA and protein, detectable in both cell types, increased markedly during cell fusion, but decreased in contracting myotubes. GLUT4 mRNA and protein were not expressed in myoblasts. They appeared only in spontaneously contracting myotubes cultured on an extracellular matrix. Insulin or IGF-I had no effect on the expression of the three glucose transporter isoforms, even in the absence of glucose. The rate of glucose transport, assessed using 2-[3H]deoxyglucose, was 2-fold higher in myotubes than in myoblasts. Glucose deprivation increased the basal rate of glucose transport by 2-fold in myoblasts, and 4-fold in myotubes. The cellular localization of the glucose transporters was directly examined by immunofluorescence staining. GLUT1 was located on the plasma membrane of myoblasts and myotubes. GLUT3 was located intracellularly in myoblasts and appeared also on the plasma membrane in myotubes. Insulin or IGF-I were unable to target GLUT3 to the plasma membrane. GLUT4, the insulin-regulatable glucose transporter isoform, appeared only in contracting myotubes in small intracellular vesicles. It was translocated to the plasma membrane after a short exposure to insulin, as it is in skeletal muscle in vivo. These results show that there is a switch in glucose transporter isoform expression during myogenic differentiation, dependent upon the energy required by the different stages of the process. GLUT3 seemed to play a role during cell fusion, and could be a marker for the muscle's ability to regenerate.

Role of myokines in exercise and metabolism

2007 ◽  
Vol 103 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Bente Klarlund Pedersen ◽  
Thorbjörn C. A. Åkerström ◽  
Anders R. Nielsen ◽  
Christian P. Fischer
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Contractile Activity ◽  
Endocrine Effects ◽  
Skeletal Muscle Function ◽  
The Past ◽  
Exercise Induced ◽  
Immune Changes ◽  
Muscle Contractile

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

scholarly journals The effects of muscle contraction and insulin on glucose-transporter translocation in rat skeletal muscle

1994 ◽  
Vol 297 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J T Brozinick ◽  
G J Etgen ◽  
B B Yaspelkis ◽  
J L Ivy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Protein Distribution ◽  
Sprague Dawley ◽  
Glut 4

The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.

Effects of ovariectomy and exercise training on muscle GLUT-4 content and glucose metabolism in rats

1996 ◽  
Vol 80 (5) ◽  
pp. 1605-1611 ◽  
Author(s):  
P. A. Hansen ◽  
T. J. McCarthy ◽  
E. N. Pasia ◽  
R. J. Spina ◽  
E. A. Gulve
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Hormone Deficiency ◽  
Ovarian Hormone ◽  
Transporter Protein ◽  
Glut 4 ◽  
Female Wistar Rats ◽  
Flexor Digitorum Brevis

The present study examined the effects of 6 wk of ovarian endocrine deficiency on skeletal muscle GLUT-4 glucose transporter protein and glucose transport activity in sedentary and endurance-trained rats. Female Wistar rats (10 wk old) underwent bilateral ovariectomy (OVX) or sham surgery followed by a 5-wk swim-training protocol. OVX resulted in no significant changes in glycogen or GLUT-4 glucose transporter concentration in the soleus, epitrochlearis, or flexor digitorum brevis (FDB) muscles or in basal and maximally insulin-stimulated 2-deoxy-D-[1,2-3H]glucose (2-[3H]DG) transport in the soleus or epitrochlearis, suggesting that moderate-duration ovarian hormone deficiency does not significantly impair insulin action in skeletal muscle. In contrast, OVX decreased the maximal activation of 2-[3H]DG transport in the FDB by in vitro electrical stimulation. OVX had no significant effect on the training-induced changes in oxidative enzyme activities, GLUT-4 protein expression, glycogen content, or insulin-stimulated 2-[3H]DG transport in the soleus or epitrochlearis. These findings provide the first evidence that ovarian hormone deficiency decreases contraction-stimulated glucose transport in skeletal muscle.

Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes

1993 ◽  
Vol 265 (1) ◽  
pp. E128-E134 ◽  
Author(s):  
B. Stallknecht ◽  
P. H. Andersen ◽  
J. Vinten ◽  
L. L. Bendtsen ◽  
J. Sibbersen ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Physical Training ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Intrinsic Activity ◽  
Mrna Levels ◽  
Glut 1 ◽  
Transporter Protein ◽  
Glut 4 ◽  
Adipocyte Volume

Physical training increases insulin-stimulated glucose transport and the number of glucose transporters in adipocytes measured by cytochalasin B binding. In the present study we used immunoblotting to measure the abundance of two glucose transporters (GLUT-4, GLUT-1) in white adipocytes from trained rats. Furthermore, the abundance of the mRNAs for these proteins and glucose transport was measured. Rats were swim-trained for 10 wk, and adipocytes were isolated from epididymal fat pads. The amount of GLUT-4/adipocyte volume unit was significantly higher in trained animals compared with both age- and cell size-matched animals. The amount of GLUT-4 mRNA was also increased by training and it decreased with increasing age. Furthermore, young age as well as training was accompanied by relatively low GLUT-4 protein/mRNA and relatively high overall GLUT-4 efficiency (recruitability and/or intrinsic activity). GLUT-1 protein and mRNA levels/adipocyte volume did not change with age or training.

Seasonal changes in plasma membrane glucose transporters enhance cryoprotectant distribution in the freeze-tolerant wood frog

1995 ◽  
Vol 73 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Patricia A. King ◽  
Mary N. Rosholt ◽  
Kenneth B. Storey
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Seasonal Changes ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Wood Frog ◽  
Maximal Velocity ◽  
Liver Membranes

One of the critical adaptations for freeze tolerance by the wood frog, Rana sylvatica, is the production of large quantities of glucose as an organ cryoprotectant during freezing exposures. Glucose export from the liver, where it is synthesized, and its uptake by other organs is dependent upon carrier-mediated transport across plasma membranes by glucose-transporter proteins. Seasonal changes in the capacity to transport glucose across plasma membranes were assessed in liver and skeletal muscle of wood frogs; summer-collected (June) frogs were compared with autumn-collected (September) cold-acclimated (5 °C for 3–4 weeks) frogs. Plasma membrane vesicles prepared from liver of autumn-collected frogs showed 6-fold higher rates of carrier-mediated glucose transport than vesicles from summer-collected frogs, maximal velocity (Vmax) values for transport being 72 ± 14 and 12.0 + 2.9 nmol∙mg protein−1∙s−1, respectively (at 10 °C). However, substrate affinity constants for carrier-mediated glucose transport (K1/2) did not change seasonally. The difference in transport rates was due to greater numbers of glucose transporters in liver plasma membranes from autumn-collected frogs. The total number of transporter sites, as determined by cytochalasin B binding, was 8.5-fold higher in autumn than in summer. Glucose transporters in wood frog liver membranes cross-reacted with antibodies to the rat GluT-2 glucose transporter (the mammalian liver isoform), and Western blots further confirmed a large increase in transporter numbers in liver membranes from autumn- versus summer-collected frogs. By contrast with the liver, however, there were no seasonal changes in glucose-transporter activity or numbers in plasma membranes isolated from skeletal muscle. We conclude that an enhanced capacity for glucose transport across liver, but not muscle, plasma membranes during autumn cold-hardening is an important adaptation that anticipates the need for rapid export of cryoprotectant from liver during natural freezing episodes.

Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters

1999 ◽  
Vol 276 (3) ◽  
pp. R809-R817 ◽  
Author(s):  
Utpala G. Das ◽  
Robert E. Schroeder ◽  
William W. Hay ◽  
Sherin U. Devaskar
Keyword(s):  
Skeletal Muscle ◽  
Gestational Age ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Time Dependent ◽  
Glut 1 ◽  
Glut 4 ◽  
Specific Effects ◽  
Glucose Transporter Proteins ◽  
Maternal Glucose

To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin-responsive (GLUT-4) glucose transporter proteins by quantitative Western blot analysis in fetal ovine insulin-insensitive (brain and liver) and insulin-sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose infusions causing fetal hyperglycemia resulted in a transient 30% increase in brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia caused a decline in brain GLUT-3, an increase in brain GLUT-1, and a subsequent decline in liver GLUT-1, with no significant change in insulin-sensitive myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations, compared with gestational age-matched sham controls. We conclude that fetal glucose transporters are subject to a time-dependent and tissue- and isoform-specific differential regulation in response to altered circulating glucose and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3) are geared toward protecting the conceptus from perturbations in substrate availability, and the adaptations in GLUT-4 are geared toward development of fetal insulin resistance.

scholarly journals Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity

2013 ◽  
Vol 115 (5) ◽  
pp. 756-764 ◽  
Author(s):  
Ceren Yarar-Fisher ◽  
C. Scott Bickel ◽  
Samuel T. Windham ◽  
Amie B. McLain ◽  
Marcas M. Bamman
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Oral Glucose ◽  
Glut 4 ◽  
Cord Injury ◽  
Glucose Ingestion

The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI ( n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher ( P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower ( P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt ( P < 0.05), and Akt phosphorylation increased robustly ( P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.

Glucose transport into rat skeletal muscle: interaction between exercise and insulin

1988 ◽  
Vol 65 (2) ◽  
pp. 909-913 ◽  
Author(s):  
H. Wallberg-Henriksson ◽  
S. H. Constable ◽  
D. A. Young ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Transport Process ◽  
Sugar Transport ◽  
Glucose Transporters ◽  
Mammalian Skeletal Muscle ◽  
Rat Skeletal Muscle ◽  
Wide Range ◽  
Exercise Induced

This study was done to evaluate the effect of insulin on sugar transport into skeletal muscle after exercise. The permeability of rat epitrochlearis muscle to 3-O-methylglucose (3-MG) was measured after exposure to a range of insulin concentrations 30, 60, and 180 min after a bout of exercise. Thirty and 60 min after exercise, the effects of exercise and insulin on 3-MG transport were additive over a wide range of insulin concentrations, with no increase in sensitivity or responsiveness to insulin. After 180 min, when approximately 66% of the exercise-induced increase in sugar transport had worn off, both the responsiveness and sensitivity of the glucose transport process to insulin were increased. These findings appear compatible with the hypothesis that the actions of exercise and insulin result in activation and/or translocation into the plasma membrane of two separate pools of glucose transporters in mammalian skeletal muscle.

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