Electrical stimulation induces fiber type-specific translocation of GLUT-4 to T tubules in skeletal muscle

1997 ◽  
Vol 273 (4) ◽  
pp. E688-E694 ◽  
Author(s):  
Denis Roy ◽  
Erlingur Jóhannsson ◽  
Arend Bonen ◽  
André Marette
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Glucose Transport ◽  
Plasma Membranes ◽  
Fiber Type ◽  
Type I ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Muscle Types ◽  
T Tubules

Insulin and contraction independently stimulate glucose transport in skeletal muscle. Whereas insulin activates glucose transport more in muscles composed of type I and IIa fibers, electrical stimulation increases glucose transport at least as much in type IIb fiber-enriched muscles despite the fact that the latter fiber type contains less GLUT-4 glucose transporters. The aim of the present study was to test the hypothesis that a greater GLUT-4 translocation to the cell surface may underlie the higher contraction-stimulated glucose transport in type IIb myofibers. Leg muscles from rats were stimulated in situ at 100 Hz (200 ms) each 2 s via the sciatic nerve over a period of 20 min while the contralateral leg was kept at rest. Muscle 2-[3H]deoxy-d-glucose uptake (2-DG) was measured in separated red gastrocnemius (RG, type I and IIa fibers) and white gastrocnemius (WG, type IIb fibers) muscles. Resting 2-DG uptake was greater in RG than WG. Electrical stimulation increased 2-DG uptake over resting values similarly in WG and RG. Fractions enriched with either plasma membranes, transverse (T) tubules, triads, or GLUT-4-enriched intracellular membranes were isolated from RG and WG using a recently developed subcellular fractionation procedure. Electrical stimulation similarly increased GLUT-4 protein content in plasma membranes of RG and WG, whereas it stimulated GLUT-4 translocation more (∼50%) in T tubules of WG than in RG. GLUT-4 content was not changed in triads of both muscle types. The increments in cell surface GLUT-4 protein levels were paralleled by significant reductions in the amount of the transporter in the intracellular membrane fractions of both muscle types (by 60% in RG and 56% in WG). It is concluded that electrically induced contraction stimulates GLUT-4 translocation more in T tubules of WG than RG. The physiological implications of this finding for glucose uptake by contracting RG and WG muscles is discussed.

Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle

1998 ◽  
Vol 274 (4) ◽  
pp. E700-E707 ◽  
Author(s):  
Xiao-Xia Han ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Plasma Membranes ◽  
Rat Muscle ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Dose Dependent Decrease ◽  
Dose Dependent

We examined the effects of epinephrine (25, 50, and 150 nM) on 1) basal and insulin-stimulated 3- O-methylglucose (3-MG) transport in perfused rat muscles and 2) GLUT-4 in skeletal muscle plasma membranes. Insulin increased glucose transport 330–600% in three types of skeletal muscle [white (WG) and red (RG) gastrocnemius and soleus (SOL)]. Glucose transport was also increased by epinephrine (22–48%) in these muscles ( P < 0.05). In contrast, the insulin-stimulated 3-MG transport was reduced by epinephrine in all three types of muscles; maximal reductions were observed at 25 nM epinephrine in WG (−25%) and RG (−32.5%). A dose-dependent decrease occurred in SOL (−27% at 25 nM; −55% at 150 nM, P < 0.05). Insulin (20 mU/ml) and epinephrine (150 nM) each translocated GLUT-4 to the plasma membrane, and no differences in translocation were observed between insulin and epinephrine ( P > 0.05). In addition, epinephrine did not inhibit insulin-stimulated GLUT-4 translocation, and the combined epinephrine and insulin effects on GLUT-4 translocation were not additive. The increase in surface GLUT-4 was associated with increases in muscle cAMP concentrations, but only when epinephrine alone was present. No relationship was evident between muscle cAMP concentrations and surface GLUT-4 in the combined epinephrine and insulin-stimulated muscles. These studies indicate that epinephrine can translocate GLUT-4 while at the same time increasing glucose transport when insulin is absent, or can inhibit glucose transport when insulin is present.

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.

A new procedure for the isolation of plasma membranes, T tubules, and internal membranes from skeletal muscle

1996 ◽  
Vol 270 (4) ◽  
pp. E667-E676 ◽  
Author(s):  
L. Dombrowski ◽  
D. Roy ◽  
B. Marcotte ◽  
A. Marette
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Plasma Membranes ◽  
Subcellular Fractionation ◽  
Intracellular Fraction ◽  
Transporter Protein ◽  
Glut 4 ◽  
T Tubules ◽  
Surface Domains

A new subcellular fractionation procedure for the simultaneous isolation of plasma membranes and transverse (T) tubule membranes from a rat skeletal muscle was developed. This new technique allows the isolation and separation of plasma membranes and T tubules in distinct subcellular fractions, as revealed by the membrane distribution of enzymatic and immunologic markers of both cell surface compartments. The procedure also yields a novel membrane fraction that is devoid of markers of both surface domains but is markedly enriched with GLUT-4 glucose transporters, thus strongly suggesting that it represents an intracellular pool of GLUT-4. Using this new procedure, we found that acute in vivo insulin administration (30 min) increased GLUT-4 protein content in the plasma membrane and a T tubule fraction (by approximately 80%), whereas a smaller elevation (35%) was observed in another fraction enriched with T tubules. Insulin induced a concomitant reduction (approximately 40%) in GLUT-4 abundance in the intracellular fraction. These results further support the hypothesis that T tubules are involved in the regulation of glucose transport in skeletal muscle. This novel fractionation method will be useful in investigating the regulation of muscle GLUT-4 transporters in other physiological and disease states such as diabetes, where defective translocation of the transporter protein to either one or both cell surface domains is suspected to occur.

Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles

2003 ◽  
Vol 94 (4) ◽  
pp. 1373-1379 ◽  
Author(s):  
Niels Jessen ◽  
Rasmus Pold ◽  
Esben S. Buhl ◽  
Lasse S. Jensen ◽  
Ole Schmitz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Exercise Group ◽  
Control Group ◽  
Glut 4

Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5′-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.

Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle

1990 ◽  
Vol 259 (6) ◽  
pp. E778-E786 ◽  
Author(s):  
T. Ploug ◽  
B. M. Stallknecht ◽  
O. Pedersen ◽  
B. B. Kahn ◽  
T. Ohkuwa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Training Session ◽  
Residual Effect ◽  
Exercise Session ◽  
Transport Capacity ◽  
Glut 1 ◽  
Glut 4 ◽  
Fast Twitch

The effect of 10 wk endurance swim training on 3-O-methylglucose (3-MG) uptake (at 40 mM 3-MG) in skeletal muscle was studied in the perfused rat hindquarter. Training resulted in an increase of approximately 33% for maximum insulin-stimulated 3-MG transport in fast-twitch red fibers and an increase of approximately 33% for contraction-stimulated transport in slow-twitch red fibers compared with nonexercised sedentary muscle. A fully additive effect of insulin and contractions was observed both in trained and untrained muscle. Compared with transport in control rats subjected to an almost exhaustive single exercise session the day before experiment both maximum insulin- and contraction-stimulated transport rates were increased in all muscle types in trained rats. Accordingly, the increased glucose transport capacity in trained muscle was not due to a residual effect of the last training session. Half-times for reversal of contraction-induced glucose transport were similar in trained and untrained muscles. The concentrations of mRNA for GLUT-1 (the erythrocyte-brain-Hep G2 glucose transporter) and GLUT-4 (the adipocyte-muscle glucose transporter) were increased approximately twofold by training in fast-twitch red muscle fibers. In parallel to this, Western blot demonstrated a approximately 47% increase in GLUT-1 protein and a approximately 31% increase in GLUT-4 protein. This indicates that the increases in maximum velocity for 3-MG transport in trained muscle is due to an increased number of glucose transporters.

Genetic and other determinants of AMP deaminase activity in healthy adult skeletal muscle

1998 ◽  
Vol 85 (4) ◽  
pp. 1273-1278 ◽  
Author(s):  
Barbara Norman ◽  
Donna K. Mahnke-Zizelman ◽  
Amy Vallis ◽  
Richard L. Sabina
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Mutant Allele ◽  
Fiber Type ◽  
Type I ◽  
Training Status ◽  
Amp Deaminase ◽  
Normal Allele ◽  
Relative Percentage ◽  
Type I Fibers

AMPD1 genotype, relative fiber type composition, training status, and gender were evaluated as contributing factors to the reported variation in AMP deaminase enzyme activity in healthy skeletal muscle. Multifactorial correlative analyses demonstrate that AMPD1 genotype has the greatest effect on enzyme activity. An AMPD1 mutant allele frequency of 13.7 and a 1.7% incidence of enzyme deficiency was found across 175 healthy subjects. Homozygotes for the AMPD1 normal allele have high enzyme activities, and heterozygotes display intermediate activities. When examined according to genotype, other factors were found to affect variability as follows: AMP deaminase activity in homozygotes for the normal allele exhibits a negative correlation with the relative percentage of type I fibers and training status. Conversely, residual AMP deaminase activity in homozygotes for the mutant allele displays a positive correlation with the relative percentage of type I fibers. Opposing correlations in different homozygous AMPD1 genotypes are likely due to relative fiber-type differences in the expression of AMPD1 and AMPD3 isoforms. Gender also contributes to variation in total skeletal muscle AMP deaminase activity, with normal homozygous and heterozygous women showing only 85–88% of the levels observed in genotype-matched men.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles

1996 ◽  
Vol 80 (2) ◽  
pp. 699-705 ◽  
Author(s):  
T. Tsakiridis ◽  
P. P. Wong ◽  
Z. Liu ◽  
C. D. Rodgers ◽  
M. Vranic ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Skeletal Muscles ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Treadmill Running ◽  
Type I ◽  
Mrna Levels ◽  
Subunit Mrna ◽  
White Type

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.

Short-term exercise enhances insulin-stimulated GLUT-4 translocation and glucose transport in adipose cells

1998 ◽  
Vol 85 (6) ◽  
pp. 2106-2111 ◽  
Author(s):  
Cynthia M. Ferrara ◽  
Thomas H. Reynolds ◽  
Mary Jane Zarnowski ◽  
Joseph T. Brozinick ◽  
Samuel W. Cushman
Keyword(s):  
Exercise Training ◽  
Cell Surface ◽  
Glucose Transport ◽  
Transport Activity ◽  
Short Term ◽  
Adipose Cell ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Adipose Cell Size ◽  
Adipose Cells

This investigation examined the effects of short-term exercise training on insulin-stimulated GLUT-4 glucose transporter translocation and glucose transport activity in rat adipose cells. Male Wistar rats were randomly assigned to a sedentary (Sed) or swim training group (Sw, 4 days; final 3 days: 2 × 3 h/day). Adipose cell size decreased significantly but minimally (∼20%), whereas total GLUT-4 increased by 30% in Sw vs. Sed rats. Basal 3- O-methyl-d-[14C]glucose transport was reduced by 62%, whereas maximally insulin-stimulated (MIS) glucose transport was increased by 36% in Sw vs. Sed rats. MIS cell surface GLUT-4 photolabeling was 44% higher in the Sw vs. Sed animals, similar to the increases observed in MIS glucose transport activity and total GLUT-4. These results suggest that increases in total GLUT-4 and GLUT-4 translocation to the cell surface contribute to the increase in MIS glucose transport with short-term exercise training. In addition, the results suggest that the exercise training-induced adaptations in glucose transport occur more rapidly than previously thought and with minimal changes in adipose cell size.

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

1997 ◽  
Vol 83 (4) ◽  
pp. 1291-1299 ◽  
Author(s):  
Michael D. Delp ◽  
Changping Duan ◽  
John P. Mattson ◽  
Timothy I. Musch
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Enzyme Activities ◽  
Fiber Type ◽  
Left Ventricular ◽  
Type I ◽  
Fiber Composition ◽  
Muscle Biochemistry ◽  
Type I Fibers

Delp, Michael D., Changping Duan, John P. Mattson, and Timothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure. J. Appl. Physiol. 83(4): 1291–1299, 1997.—One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls ( n = 13) and rats with moderate ( n = 10) and severe ( n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations ( P < 0.05) in left ventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD, 11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and β-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

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