Regulation of Glucose Transporters and the Na/K-ATPase by Insulin in Skeletal Muscle

1993 ◽  
pp. 63-78 ◽  
Author(s):  
Harinder S. Hundal ◽  
Amira Klip
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transporters

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.

scholarly journals Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle

1996 ◽  
Vol 313 (1) ◽  
pp. 215-222 ◽  
Author(s):  
Jiri TURINSKY ◽  
G. William NAGEL ◽  
Jeffrey S. ELMENDORF ◽  
Alice DAMRAU-ABNEY ◽  
Terry R. SMITH
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Cytochalasin B ◽  
Glucose Transporters ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Receptor Tyrosine Kinase ◽  
Cellular Accumulation ◽  
C6 Ceramide ◽  
Phosphatidylinositol 3

The effects of sphingomyelinase, phosphorylcholine, N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or 200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and that at 0.1 and 1.0 m-unit of insulin/ml by 32-82% and 19-25% respectively compared with control muscles studied at the same insulin concentrations. The sphingomyelinase-induced increase in basal and insulin-stimulated 2-deoxyglucose uptake was inhibited by 91% by 70 μM cytochalasin B, suggesting that it involves glucose transporters. Sphingomyelinase had no effect on the cellular accumulation of L-glucose, which is not transported by glucose transporters. The sphingomyelinase-induced increase in 2-deoxyglucose uptake could not be reproduced by preincubating the muscles with 50 μM phosphorylcholine, 50 μM C2-ceramide or 50 μM C6-ceramide. Preincubation of muscles with 50 μM sphingosine augmented basal 2-deoxyglucose transport by 32%, but reduced the response to 0.1 and 1.0 m-unit of insulin/ml by 17 and 27% respectively. The stimulatory effect of sphingomyelinase on basal and insulin-induced 2-deoxyglucose uptake was not influenced by either removal of Ca2+ from the incubation medium or dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum. This demonstrates that Ca2+ does not mediate the action of sphingomyelinase on 2-deoxyglucose uptake. Sphingomyelinase also had no effect on basal and insulin-stimulated activities of insulin receptor tyrosine kinase and phosphatidylinositol 3-kinase. In addition, 1 and 5 μM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, failed to inhibit the sphingomyelinase-induced increase in 2-deoxyglucose uptake. These results suggest that sphingomyelinase does not increase 2-deoxyglucose uptake by stimulating the insulin receptor or the initial steps of the insulin-transduction pathway. The data suggest the possibility that sphingomyelinase increases basal and insulin-stimulated 2-deoxyglucose uptake in skeletal muscle as the result of an unknown post-receptor effect.

scholarly journals Identification and Characterization of an Exercise-sensitive Pool of Glucose Transporters in Skeletal Muscle

1995 ◽  
Vol 270 (46) ◽  
pp. 27584-27588 ◽  
Author(s):  
Lise Coderre ◽  
Konstantin V. Kandror ◽  
Gino Vallega ◽  
Paul F. Pilch
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transporters ◽  
Identification And Characterization

scholarly journals Acute exercise increases the number of plasma membrane glucose transporters in rat skeletal muscle

FEBS Letters ◽  
1988 ◽  
Vol 238 (2) ◽  
pp. 235-239 ◽  
Author(s):  
Michael F. Hirshman ◽  
Harriet Wallberg-Henriksson ◽  
Lawrence J. Wardzala ◽  
Elizabeth D. Horton ◽  
Edward S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Acute Exercise ◽  
Glucose Transporters ◽  
Rat Skeletal Muscle

scholarly journals Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia.

1992 ◽  
Vol 3 (5) ◽  
pp. 1078-1091
Author(s):  
D Dimitrakoudis ◽  
M Vranic ◽  
A Klip
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Cytochalasin B ◽  
Glucose Transporters ◽  
Whole Body ◽  
Partial Recovery ◽  
Peripheral Tissues ◽  
Glucose Levels ◽  
Glucose Reabsorption ◽  
Insulin Dependent

Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)

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