Exercise- and Insulin-Stimulated Muscle Glucose Transport: Distinct Mechanisms of Regulation

2002 ◽  
Vol 27 (2) ◽  
pp. 129-151 ◽  
Author(s):  
Zayna A. Khayat ◽  
Nish Patel ◽  
Amira Klip
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Energy Demand ◽  
Glucose Transporter ◽  
Current Knowledge ◽  
Glucose Transporters ◽  
Phosphatidylinositol 3 Kinase ◽  
Alternative Pathways ◽  
Muscle Glucose Transport ◽  
L6 Muscle Cells

In mammals, skeletal muscle is the primary target for the stimulation of glucose transport by a variety of activators. These include the hormone insulin and stimuli which increase energy demand such as exercise, hypoxia, and challenges to the oxidative chain. While it is known that both stimuli rapidly elevate glucose uptake into muscle by signalling the translocation of glucose transporters from intracellular stores to the plasma membrane, there are numerous contrasts between energy stressors and insulin in their mechanisms of glucose transport activation. Exercise and insulin recruit distinct intracellular pools of glucose transporters in skeletal muscle and the maximal effects of contraction and insulin are additive. Activation of phosphatidylinositol 3-kinase (PI3-K) is utilized by insulin to induce glucose transporter translocation, but does not participate in the responses to exercise or hypoxia. These findings suggest that energy stressors utilize different mechanisms from insulin to increase glucose influx; however, how these factors elicit their response is not clear. This review will summarize our current knowledge of these alternative pathways of glucose transport regulation. Emphasis is placed on the use of the mitochondrial uncoupler dinitrophenol to investigate mediators of this alternative signalling pathway in L6 muscle cells, a line used to characterize physiological responses in muscle such as glucose transport. Key words: contraction, GLUT4, cPKC, Ca2+, AMPK

scholarly journals Skeletal Muscle Glucose Transport and Metabolism Are Enhanced in Transgenic Mice Overexpressing the Glut4 Glucose Transporter.

1995 ◽  
Vol 270 (4) ◽  
pp. 1679-1684
Author(s):  
Polly A. Hansen ◽  
Eric A. Gulve ◽  
Bess Adkins Marshall ◽  
Jiaping Gao ◽  
Jeffrey E. Pessin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Muscle Glucose Transport

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.

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.

Voluntary exercise training enhances glucose transport but not insulin signaling capacity in muscle of hypertensive TG(mREN2)27 rats

2005 ◽  
Vol 99 (1) ◽  
pp. 357-362 ◽  
Author(s):  
Andrew M. Lemieux ◽  
Cody J. Diehl ◽  
Julie A. Sloniger ◽  
Erik J. Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Glycogen Synthase ◽  
Abdominal Fat ◽  
Voluntary Exercise ◽  
Phosphatidylinositol 3 Kinase ◽  
Muscle Glucose Transport

Male heterozygous TG(mREN2)27 rats (TGR) overexpress a murine renin transgene, display marked hypertension, and have insulin resistance of skeletal muscle glucose transport and insulin signaling. We have shown previously that voluntary exercise training by TGR improves insulin-mediated skeletal muscle glucose transport (Kinnick TR, Youngblood EB, O’Keefe MP, Saengsirisuwan V, Teachey MK, and Henriksen EJ. J Appl Physiol 93: 805–812, 2002). The present study evaluated whether this training-induced enhancement of muscle glucose transport is associated with upregulation of critical insulin signaling elements, including insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase, Akt, and glycogen synthase kinase-3. TGR remained sedentary or ran spontaneously in activity wheels for 6 wk, averaging 7.1 ± 0.8 km/day by the end of week 3 and 4.3 ± 0.5 km/day over the final week of training. Exercise training reduced total abdominal fat by 20% ( P < 0.05) in TGR runners (2.64 ± 0.01% of body weight) compared with sedentary TGR controls (3.28 ± 0.01%). Insulin-stimulated (2 mU/ml) glucose transport activity in soleus muscle was 36% greater in TGR runners compared with sedentary TGR controls. However, the protein expression and functionality of tyrosine phosphorylation of insulin receptor and IRS-1, IRS-1 associated with the p85 regulatory subunit of phosphatidylinositol 3-kinase, and Ser473 phosphorylation of Akt were not altered by exercise training. Only insulin-stimulated glycogen synthase kinase-3β Ser9 phosphorylation was increased (22%) by exercise training. These results indicate that voluntary exercise training in TGR can enhance insulin-mediated glucose transport in skeletal muscle, as well as reduce total abdominal fat mass. However, this adaptive response in muscle occurs independently of modifications in the proximal elements of the insulin signaling cascade.

Effects of maturation and aging on the skeletal muscle glucose transport system

1992 ◽  
Vol 262 (5) ◽  
pp. E619-E626 ◽  
Author(s):  
R. J. Barnard ◽  
L. O. Lawani ◽  
D. A. Martin ◽  
J. F. Youngren ◽  
R. Singh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Kinase Activity ◽  
Age Groups ◽  
Insulin Receptors ◽  
Glucose Transporters ◽  
Glucose Transport System ◽  
Significant Difference ◽  
Old Rats ◽  
Muscle Glucose Transport

Insulin resistance in old, compared with young, humans and animals has been well documented. The resistance is due primarily to defects in skeletal muscle. In the present study, skeletal muscle sarcolemmal membranes were purified from five age groups of female Fischer rats ranging from 2 to 24 mo. Basal specific D-glucose transport was not significantly different among any of the groups. Maximum insulin-stimulated transport was progressively decreased from 96.4 +/- 5.0 pmol.mg-1.15 s-1 in the 2-mo-old animals to 70.8 +/- 8.9 pmol.mg-1.15 s-1 in the 24-mo-old animals. Most of the decrease occurred during maturation, and in fact there was no significant difference in maximum transport among the 8-, 16-, and 24-mo-old rats. The decrease in insulin-stimulated transport in the 24-mo-old animals was due to a reduction in the number of glucose transporters translocated into the sarcolemma membrane (9.8 +/- 0.6 vs. 7.8 +/- 0.6 pmol/mg protein). The intracellular or microsomal pool of glucose transporters was not significantly different between the 2- and 24-mo-old animals (8.8 +/- 0.6 vs. 8.5 +/- 0.9/mg protein). Western blotting revealed no differences in the cellular GLUT-4 contents between the 2- and 24-mo-old rats. The number of insulin receptors (2.3 +/- 0.4 vs. 2.1 +/- 0.5 pmol/mg protein) was not significantly different. Tyrosine kinase activity of the insulin receptor was, however, significantly reduced in the 24-mo-old compared with the 2-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization

1996 ◽  
Vol 315 (3) ◽  
pp. 959-963 ◽  
Author(s):  
Raffaele NAPOLI ◽  
Antonio CITTADINI ◽  
Jesse C. CHOW ◽  
Michael F. HIRSHMAN ◽  
Robert J. SMITH ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Growth Hormone Treatment ◽  
Membrane Vesicles ◽  
Hormone Treatment ◽  
Plasma Membrane Vesicles ◽  
Muscle Glucose Transport

Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg/kg per day) would impair glucose transport and/or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of Sprague–Dawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (Vmax or Km) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (Ro) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (Vmax/Ro), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and control rats. hGH did not change GLUT4 protein content in whole muscle or in the plasma membrane, and muscle content of GLUT4 mRNA also was unchanged. In contrast, GLUT1 protein content in the plasma membrane fraction was significantly reduced by hGH treatment. This was associated with a modest, although not significant, decrease in muscle content of GLUT1 mRNA. In conclusion, high-dose hGH treatment for 4 weeks did not alter post-prandial skeletal muscle glucose transport activity. Neither the muscle level nor the intracellular localization of GLUT4 was changed by the hormone treatment. On the contrary, the basal post-prandial level of GLUT1 in the plasma membrane was reduced by hGH. The mRNA data suggest that this reduction might result from a decrease in the synthesis of GLUT1.

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