Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle

1991 ◽  
Vol 70 (5) ◽  
pp. 2322-2327 ◽  
Author(s):  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
C. E. Mondon ◽  
D. E. James ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Muscle Activity ◽  
Glucose Transporter ◽  
Major Contributor ◽  
Transporter Protein ◽  
Glut 4 ◽  
Rat Soleus Muscle ◽  
Stimulation Of

The purpose of this study was to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). One day after sciatic nerve sectioning, when decreases in the stimulation of soleus 2-deoxyglucose (2-DG) uptake by insulin (-51%, P less than 0.001), contractions (-29%, P less than 0.05), or insulin and contractions in combination (-40%, P less than 0.001) were observed, there was a slight (-18%, NS) decrease in GLUT-4 protein. By day 3 of denervation, stimulation of 2-DG uptake by insulin (-74%, P less than 0.001), contractions (-31%, P less than 0.001), or the two stimuli in combination (-59%, P less than 0.001), as well as GLUT-4 protein (-52%, P less than 0.001), was further reduced. Soleus muscle from hindlimb-suspended rats, which develops an enhanced capacity for insulin-stimulated glucose transport, showed muscle atrophy similar to denervated soleus but, in contrast, displayed substantial increases in GLUT-4 protein after 3 (+35%, P less than 0.05) and 7 days (+107%, P less than 0.001). These results indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. We conclude that muscle activity is an important factor in the regulation of GLUT-4 expression in skeletal muscle.

scholarly journals Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes

1990 ◽  
Vol 269 (3) ◽  
pp. 597-601 ◽  
Author(s):  
D M Calderhead ◽  
K Kitagawa ◽  
G E Lienhard ◽  
G W Gould
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Fold Increase ◽  
The Other ◽  
Insulin Stimulation ◽  
Glut 1 ◽  
Glut 4 ◽  
Rat Soleus Muscle ◽  
The Brain ◽  
Stimulation Of

Insulin-stimulated glucose transport was examined in BC3H-1 myocytes. Insulin treatment lead to a 2.7 +/- 0.3-fold increase in the rate of deoxyglucose transport and, under the same conditions, a 2.1 +/- 0.1-fold increase in the amount of the brain-type glucose transporter (GLUT 1) at the cell surface. It has been shown that some insulin-responsive tissues express a second, immunologically distinct, transporter, namely GLUT 4. We report here that BC3H-1 myocytes and C2 and G8 myotubes express only GLUT 1; in contrast, rat soleus muscle and heart express 3-4 times higher levels of GLUT 4 than GLUT 1. Thus translocation of GLUT 1 can account for most, if not all, of the insulin stimulation of glucose transport in BC3H-1 myocytes. On the other, hand, neither BC3H-1 myocytes nor the other muscle-cell lines are adequate as models for the study of insulin regulation of glucose transport in muscle tissue.

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.

Muscle insulin resistance in uremic humans: glucose transport, glucose transporters, and insulin receptors

1991 ◽  
Vol 261 (1) ◽  
pp. E87-E94 ◽  
Author(s):  
J. E. Friedman ◽  
G. L. Dohm ◽  
C. W. Elton ◽  
A. Rovira ◽  
J. J. Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Insulin Receptors ◽  
Glucose Disposal ◽  
Intravenous Glucose ◽  
Transporter Protein ◽  
Glut 4 ◽  
Uremic Patients

To determine the cellular basis for insulin resistance observed in patients with uremia, we investigated insulin action in vivo and in vitro using skeletal muscle obtained from patients with chronic renal failure. Uremic subjects had significantly reduced rates of insulin-stimulated glucose disposal, as determined by a 3-h intravenous glucose tolerance test and using the hyperinsulinemic euglycemic clamp technique. Hepatic glucose production was similar before (control, 76.2 +/- 6.3 vs. uremic, 74.2 +/- 6.9 mg.kg-1.min-1) and during insulin infusion at 40 mU.m-2.min-1 (control, -60.9 +/- 6.6 vs. uremic, -53.9 +/- 6.3 mg.kg-1.min-1). In incubated human skeletal muscle fiber strips, basal 2-deoxy-D-glucose transport was unchanged in uremic subjects compared with controls. However, the increase in insulin-stimulated glucose transport was significantly reduced by 50% in muscles from uremic patients (P = 0.012). In partially purified insulin receptors prepared from skeletal muscle, 125I-labeled insulin binding, beta-subunit receptor autophosphorylation, and tyrosine kinase activity were all unchanged in uremic subjects. The abundance of insulin-sensitive (muscle/fat, GLUT-4) glucose transporter protein measured by Western blot using Mab 1F8 or polyclonal antisera was similar in muscles of control and uremic patients. These findings suggest that the insulin resistance observed in skeletal muscle of uremic patients cannot be attributed to defects in insulin receptor function or depletion of the GLUT-4 glucose transporter protein. An alternative step in insulin-dependent activation of the glucose transport process may be involved.

Calorie restriction increases cell surface GLUT-4 in insulin-stimulated skeletal muscle

1998 ◽  
Vol 275 (6) ◽  
pp. E957-E964 ◽  
Author(s):  
David J. Dean ◽  
Joseph T. Brozinick ◽  
Samuel W. Cushman ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Glucose Transport ◽  
Calorie Restriction ◽  
Glucose Transporter ◽  
Calorie Intake ◽  
Phosphatidylinositol 3 Kinase ◽  
Glut 4 ◽  
Pi3k Activity ◽  
Stimulation Of

Reduced calorie intake [calorie restriction (CR); 60% of ad libitum (AL)] leads to enhanced glucose transport without altering total GLUT-4 glucose transporter abundance in skeletal muscle. Therefore, we tested the hypothesis that CR (20 days) alters the subcellular distribution of GLUT-4. Cell surface GLUT-4 content was higher in insulin-stimulated epitrochlearis muscles from CR vs. AL rats. The magnitude of this increase was similar to the CR-induced increase in glucose transport, and GLUT-4 activity (glucose transport rate divided by cell surface GLUT-4) was unaffected by diet. The CR effect was specific to the insulin-mediated pathway, as evidenced by the observations that basal glucose transport and cell surface GLUT-4 content, as well as hypoxia-stimulated glucose transport, were unchanged by diet. CR did not alter insulin’s stimulation of insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity. Muscle abundance of IRS-2 and p85 subunit of PI3K were unaltered by diet, but IRS-1 content was lower in CR vs. AL. These data demonstrate that, despite IRS-1-PI3K activity similar to AL, CR specifically increases insulin’s activation of glucose transport by enhancing the steady-state proportion of GLUT-4 residing on the cell surface.

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.

Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle

1997 ◽  
Vol 273 (3) ◽  
pp. C1082-C1087 ◽  
Author(s):  
A. D. Lee ◽  
P. A. Hansen ◽  
J. Schluter ◽  
E. A. Gulve ◽  
J. Gao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Inhibitory Effect ◽  
Phosphate Concentration ◽  
Intrinsic Activity ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Glut 4

beta-Adrenergic stimulation has been reported to inhibit insulin-stimulated glucose transport in adipocytes. This effect has been attributed to a decrease in the intrinsic activity of the GLUT-4 isoform of the glucose transporter that is mediated by phosphorylation of GLUT-4. Early studies showed no inhibition of insulin-stimulated glucose transport by epinephrine in skeletal muscle. The purpose of this study was to determine the effect of epinephrine on GLUT-4 phosphorylation, and reevaluate the effect of beta-adrenergic stimulation on insulin-activated glucose transport, in skeletal muscle. We found that 1 microM epinephrine, which raised adenosine 3',5'-cyclic monophosphate approximately ninefold, resulted in GLUT-4 phosphorylation in rat skeletal muscle but had no inhibitory effect on insulin-stimulated 3-O-methyl-D-glucose (3-MG) transport. In contrast to 3-MG transport, the uptakes of 2-deoxyglucose and glucose were markedly inhibited by epinephrine treatment. This inhibitory effect was presumably mediated by stimulation of glycogenolysis, which resulted in an increase in glucose 6-phosphate concentration to levels known to severely inhibit hexokinase. We conclude that 1) beta-adrenergic stimulation decreases glucose uptake by raising glucose 6-phosphate concentration, thus inhibiting hexokinase, but does not inhibit insulin-stimulated glucose transport and 2) phosphorylation of GLUT-4 has no effect on glucose transport in skeletal muscle.

Effect of diet on insulin- and contraction-mediated glucose transport and uptake in rat muscle

1995 ◽  
Vol 269 (3) ◽  
pp. R544-R551 ◽  
Author(s):  
X. Han ◽  
T. Ploug ◽  
H. Galbo
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Fiber Types ◽  
Transport Capacity ◽  
Glut 1 ◽  
Glut 4 ◽  
Red Muscle ◽  
Muscle Glucose Transport ◽  
Stimulation Of

A diet rich in fat diminishes insulin-mediated glucose uptake in muscle. This study explored whether contraction-mediated glucose uptake is also affected. Rats were fed a diet rich in fat (FAT, 73% of energy) or carbohydrate (CHO, 66%) for 5 wk. Hindquarters were perfused, and either glucose uptake or glucose transport capacity (uptake of 3-O-[14C]-methyl-D-glucose (40 mM)) was measured. Amounts of glucose transporter isoform GLUT-1 and GLUT-4 glucose-transporting proteins were determined by Western blot. Glucose uptake was lower (P < 0.05) in hindlegs from FAT than from CHO rats at submaximum and maximum insulin [4 +/- 0.4 vs. 5 +/- 0.3 (SE) mumol.min-1.leg-1 at 150 microU/ml insulin] as well as during prolonged stimulation of the sciatic nerve (4.4 +/- 0.4 vs. 5.6 +/- 0.6 mumol.min-1.leg-1). Maximum glucose transport elicited by insulin (soleus: 1.7 +/- 0.2 vs. 2.6 +/- 0.2 mumol.g-1.5 min-1, P < 0.05) or contractions (soleus: 1.8 +/- 0.2 vs. 2.6 +/- 0.3, P < 0.05) in red muscle was decreased in parallel in FAT compared with CHO rats. GLUT-4 content was decreased by 13-29% (P < 0.05) in the various fiber types, whereas GLUT-1 content was identical in FAT compared with CHO rats. It is concluded that a FAT diet reduces both insulin and contraction stimulation of glucose uptake in muscle and that these effects are associated with diminished skeletal muscle glucose transport capacities and GLUT-4 contents.

scholarly journals Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro

1998 ◽  
Vol 139 (1) ◽  
pp. 118-122 ◽  
Author(s):  
G Dimitriadis ◽  
B Leighton ◽  
M Parry-Billings ◽  
C Tountas ◽  
S Raptis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Transport Process ◽  
Glucose Utilization ◽  
Glucose Disposal ◽  
Rat Soleus Muscle ◽  
Lactate Formation

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.

Stimulation of glucose transport in skeletal muscle by hypoxia

1991 ◽  
Vol 70 (4) ◽  
pp. 1593-1600 ◽  
Author(s):  
G. D. Cartee ◽  
A. G. Douen ◽  
T. Ramlal ◽  
A. Klip ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscle Contraction ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Sugar Transport ◽  
Transport Activity ◽  
Hindlimb Muscles ◽  
Stimulation Of

Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia.

Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle

1987 ◽  
Vol 252 (4) ◽  
pp. E492-E499 ◽  
Author(s):  
T. Clausen ◽  
J. A. Flatman
Keyword(s):  
Glucose Transport ◽  
Soleus Muscle ◽  
Sugar Transport ◽  
Resting Membrane Potential ◽  
Exchange System ◽  
Glucose Transport System ◽  
Rat Soleus Muscle ◽  
Possible Cause ◽  
K Transport ◽  
Stimulation Of

To identify possible cause-effect relationships between changes in active Na+-K+ transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in sugar transport. Ouabain, at a concentration (10(-3) M) sufficient to block active Na+-K+ transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na+ loading in K+-free buffer, the return to K+-containing standard buffer caused marked stimulation of active Na+-K+ transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the Na+-K+ pump leads to decreased intracellular Na+ concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na+-K+ transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na+ influx via the Na+/H+-exchange system.

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