Exploring the whereabouts of GLUT4 in skeletal muscle (Review)

Ploug, Thorkil; Ralston, Evelyn

doi:10.1080/09687680110119229

Cited by 21 publications

(21 citation statements)

References 109 publications

(109 reference statements)

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“…57 Other potential mechanisms for better glucose control include improvement in insulin sensitivity 58,59 and effects on glucose transporters (eg, GLUT4). 60 -64 Muscle contractions can elicit movement of glucose transporters (GLUT4) to the plasma membrane independently of insulin, [65][66][67] and it is further speculated that muscle hypertrophy 30,40,51,68 and blood flow 69 are also contributing mechanisms.…”

Section: Glycemic Controlmentioning

confidence: 99%

Exercise Training for Type 2 Diabetes Mellitus

Marwick¹,

Hordern²,

Miller³

et al. 2009

Circulation

318

133

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Section: Glycemic Controlmentioning

confidence: 99%

Exercise Training for Type 2 Diabetes Mellitus

Marwick¹,

Hordern²,

Miller³

et al. 2009

Circulation

318

133

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“…First, generally data can only be sampled at few time points, typically basal and 30 min after insulin stimulation (3)(4)(5), thereby missing intermediate GLUT4 trafficking. Second, in studies relying on subcellular fractionation or morphological GLUT4 translocation analysis, the effect of insulin can only be evaluated by comparisons between different muscles and not within single muscle fibers (4,6). Third, traditional methods are all invasive and may not accurately reflect in vivo conditions.…”

mentioning

confidence: 99%

Imaging of Insulin Signaling in Skeletal Muscle of Living Mice Shows Major Role of T-Tubules

et al. 2006

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Insulin stimulates glucose transport in skeletal muscle by glucose transporter GLUT4 translocation to sarcolemma and membrane invaginations, the t-tubules. Although muscle glucose uptake plays a key role in insulin resistance and type 2 diabetes, the dynamics of GLUT4 translocation and the signaling involved are not well described. We have now developed a confocal imaging technique to follow trafficking of green fluorescent protein-labeled proteins in living muscle fibers in situ in anesthetized mice. Using this technique, by imaging the dynamics of GLUT4 translocation and phosphatidylinositol 3,4,5 P 3 (PIP 3 ) production in response to insulin, here, for the first time, we delineate the temporal and spatial distribution of these processes in a living animal. We find a 10-min delay of maximal GLUT4 recruitment and translocation to t-tubules compared with sarcolemma. Time-lapse imaging of a fluorescent dye after intravenous injection shows that this delay is similar to the time needed for insulin diffusion into the t-tubule system. Correspondingly, immunostaining of muscle fibers shows that insulin receptors are present throughout the t-tubule system. Finally, PIP 3 production, an early event in insulin signaling, progresses slowly along the t-tubules with a 10-min delay between maximal PIP 3 production at sarcolemma compared with deep t-tubules following the appearance of dye-labeled insulin. Our findings in living mice indicate a major role of the t-tubules in insulin signaling in skeletal muscle and show a diffusion-associated delay in insulin action between sarcolemma and inner t-tubules. Diabetes 55:1300 -1306, 2006 S keletal muscle is a key regulator of glucose homeostasis, and defects in glucose uptake in muscle are central in insulin resistance and type 2 diabetes. The GLUT4 glucose transporter in skeletal muscle fibers mediates glucose uptake by translocation from intracellular compartments to the plasma membrane upon stimulation with insulin (1,2). However, the intracellular trafficking of GLUT4 in muscle and the signaling regulating these processes are poorly understood. The lack of understanding reflects the weakness of current methods for analyzing insulin-mediated GLUT4 translocation in skeletal muscle. First, generally data can only be sampled at few time points, typically basal and 30 min after insulin stimulation (3-5), thereby missing intermediate GLUT4 trafficking. Second, in studies relying on subcellular fractionation or morphological GLUT4 translocation analysis, the effect of insulin can only be evaluated by comparisons between different muscles and not within single muscle fibers (4,6). Third, traditional methods are all invasive and may not accurately reflect in vivo conditions. To overcome these problems, we have developed confocal time-lapse imaging techniques for monitoring dynamic changes in localization of green fluorescent protein (GFP)-tagged proteins in skeletal muscle fibers in situ in living mice (7) (Fig. 1). Here, using these techniques, we reveal previously unnoticed signali...

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“…In the case of glucose uptake in adipose and striated muscle, the insulin-responsive glucose transporter protein-4 (GLUT4) 2 is predominantly localized to intracellular membrane compartments and undergoes a dramatic redistribution to the cell surface following insulin stimulation through a process termed translocation (1)(2)(3)(4)(5). It has become increasingly apparent that the actin cytoskeleton and its dynamic rearrangement and remodeling are involved in the intracellular trafficking of many proteins including GLUT4 translocation (6 -16).…”

mentioning

confidence: 99%

Dual Regulation of Rho and Rac by p120 Catenin Controls Adipocyte Plasma Membrane Trafficking

Hou

Shigematsu

Crawford

et al. 2006

Journal of Biological Chemistry

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During 3T3L1 adipogenesis there is a marked reduction in ␤-catenin and N-cadherin expression with a relatively small decrease in p120 catenin protein levels. Cell fractionation demonstrated a predominant decrease in the particulate (membrane-bound) pool of p120 catenin with little effect on the soluble pool, resulting in a large redistribution from the plasma membrane to the cytosol. Reexpression of p120 catenin inhibited constitutive (transferrin receptor) and regulated mannose 6-phosphate receptor and GLUT4 trafficking to the plasma membrane. The inhibition of membrane trafficking was specific for p120 catenin function as this could be rescued by co-expression of N-cadherin. Moreover, overexpression of a p120 catenin deletion mutant (p120⌬622-628) or splice variant (p120-4A), neither of which could regulate Rho or Rac activity, showed no significant effect. The inhibition of GLUT4 translocation was also observed upon the simultaneous expression of a constitutively active Rac mutant (Rac1/Val 12 ) in combination with a dominant-interfering Rho mutant (RhoA/Asn 19 ). This was recapitulated by expression of the Rho ADP-ribosylation factor (C3ADP) in combination with constitutively active Rac1/Val 12 . Moreover, siRNA-mediated knockdown of p120 catenin resulted in increased basal state accumulation of GLUT4 at the plasma membrane. Together, these data demonstrate that p120 catenin plays an important role in maintaining the basal tone of membrane protein trafficking in adipocytes through the dual regulation of Rho and Rac function and accounts for reports implicating Rho or Rac in the control of GLUT4 translocation.The mechanisms and intracellular signaling pathways that regulate intracellular membrane trafficking are quite complex. In the case of glucose uptake in adipose and striated muscle, the insulin-responsive glucose transporter protein-4 (GLUT4) 2 is predominantly localized to intracellular membrane compartments and undergoes a dramatic redistribution to the cell surface following insulin stimulation through a process termed translocation (1-5). It has become increasingly apparent that the actin cytoskeleton and its dynamic rearrangement and remodeling are involved in the intracellular trafficking of many proteins including GLUT4 translocation (6 -16). For example, treatment of adipocytes with actin-depolymerizing agents cytochalasin D and latrunculin A or B and the actin-stabilizing agent jaspolakinolide inhibits insulin-stimulated GLUT4 translocation (6,(17)(18)(19)(20). In addition, insulin-induced dynamic actin remodeling has been observed at the inner surface of the plasma membrane and in the perinuclear region in differentiated 3T3L1 adipocytes, which is prevented by the Rho-selective Clostridium difficile toxin B (6). Currently, Cdc42, Rac1, and RhoA have been most extensively characterized and shown to regulated filopodia, lamellipodia, and stress fiber/focal adhesion formation, respectively. Several studies have also implicated Cdc42, Rac1, and RhoA as critical components in mediating insulin-stimu...

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Exploring the whereabouts of GLUT4 in skeletal muscle (Review)

Cited by 21 publications

References 109 publications

Exercise Training for Type 2 Diabetes Mellitus

Exercise Training for Type 2 Diabetes Mellitus

Imaging of Insulin Signaling in Skeletal Muscle of Living Mice Shows Major Role of T-Tubules

Dual Regulation of Rho and Rac by p120 Catenin Controls Adipocyte Plasma Membrane Trafficking

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