Slc2a4

Summary

Gene Symbol: Slc2a4
Description: solute carrier family 2 (facilitated glucose transporter), member 4
Alias: GT2, Glut-4, Glut4, twgy, solute carrier family 2, facilitated glucose transporter member 4, glucose transporter type 4, insulin-responsive
Species: mouse
Products:     Slc2a4

Top Publications

  1. Bogan J, Hendon N, McKee A, Tsao T, Lodish H. Functional cloning of TUG as a regulator of GLUT4 glucose transporter trafficking. Nature. 2003;425:727-33 pubmed
    Insulin stimulates glucose uptake in fat and muscle by mobilizing the GLUT4 glucose transporter...
  2. Widberg C, Bryant N, Girotti M, Rea S, James D. Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation. J Biol Chem. 2003;278:35093-101 pubmed
    ..and the SM protein Munc18c, in vitro, and the potential involvement of Tomosyn in regulating the translocation of GLUT4 containing vesicles, in vivo...
  3. Gonzalez E, McGraw T. Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment/docking and the fusion of GLUT4 vesicles to the plasma membrane. Mol Biol Cell. 2006;17:4484-93 pubmed
    Insulin modulates glucose disposal in muscle and adipose tissue by regulating the cellular redistribution of the GLUT4 glucose transporter...
  4. Kanzaki M, Furukawa M, Raab W, Pessin J. Phosphatidylinositol 4,5-bisphosphate regulates adipocyte actin dynamics and GLUT4 vesicle recycling. J Biol Chem. 2004;279:30622-33 pubmed
    ..potential role of phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) in the regulation of actin polymerization and GLUT4 translocation, the type I phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) were expressed in 3T3L1 adipocytes...
  5. Yip M, Ramm G, Larance M, Hoehn K, Wagner M, Guilhaus M, et al. CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes. Cell Metab. 2008;8:384-98 pubmed publisher
    The unconventional myosin Myo1c has been implicated in insulin-regulated GLUT4 translocation to the plasma membrane in adipocytes. We show that Myo1c undergoes insulin-dependent phosphorylation at S701...
  6. Dalen K, Ulven S, Bamberg K, Gustafsson J, Nebb H. Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha. J Biol Chem. 2003;278:48283-91 pubmed
    The insulin-responsive glucose transporter GLUT4 plays a crucial role in insulin-mediated facilitated glucose uptake into adipose tissue and muscle, and impaired expression of GLUT4 has been linked to obesity and diabetes...
  7. Mari M, Monzo P, Kaddai V, Keslair F, Gonzalez T, Le Marchand Brustel Y, et al. The Rab4 effector Rabip4 plays a role in the endocytotic trafficking of Glut 4 in 3T3-L1 adipocytes. J Cell Sci. 2006;119:1297-306 pubmed
    Insulin regulates glucose uptake in the adipocytes by modulating Glut 4 localization, a traffic pathway involving the endocytic small GTPases Rab4, Rab5, and RabThe expression of the Rab4 effector Rabip4 leads to a 30% increase in glucose ..
  8. Shen H, Zhang Y, Ding H, Wang X, Chen L, Jiang H, et al. Farnesoid X receptor induces GLUT4 expression through FXR response element in the GLUT4 promoter. Cell Physiol Biochem. 2008;22:1-14 pubmed publisher
    b>GLUT4, the main insulin-responsive glucose transporter, plays a critical role in maintaining systemic glucose homeostasis and is subject to complicated metabolic regulation...
  9. Fulcher F, Smith B, Russ M, Patel Y. Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Exp Cell Res. 2008;314:3264-74 pubmed publisher
    ..glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane...

More Information

Publications99

  1. Li J, Malaby A, Famulok M, Sabe H, Lambright D, Hsu V. Grp1 plays a key role in linking insulin signaling to glut4 recycling. Dev Cell. 2012;22:1286-98 pubmed publisher
    The glucose transporter type 4 (glut4) is critical for metabolic homeostasis. Insulin regulates glut4 by modulating its expression on the cell surface. This regulation is mainly achieved by targeting the endocytic recycling of glut4...
  2. Kotani K, Peroni O, Minokoshi Y, Boss O, Kahn B. GLUT4 glucose transporter deficiency increases hepatic lipid production and peripheral lipid utilization. J Clin Invest. 2004;114:1666-75 pubmed
    ..To understand the metabolic adaptations this elicits, we generated mice with targeted disruption of the GLUT4 glucose transporter in both adipocytes and muscle (AMG4KO)...
  3. Abel E, Graveleau C, Betuing S, Pham M, Reay P, Kandror V, et al. Regulation of insulin-responsive aminopeptidase expression and targeting in the insulin-responsive vesicle compartment of glucose transporter isoform 4-deficient cardiomyocytes. Mol Endocrinol. 2004;18:2491-501 pubmed
    In adipocytes and cardiac or skeletal muscle, glucose transporter isoform 4 (GLUT4) is targeted to insulin-responsive intracellular membrane vesicles (IRVs) that contain several membrane proteins, including insulin-responsive ..
  4. Machado U, Shimizu I, Saito M. Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice. Physiol Behav. 1994;55:621-5 pubmed
    We investigated glucose transporters (GLUT 1 and GLUT 4) in subcellular membrane fractions of white adipose tissue (WAT) of insulin-resistant obese aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice...
  5. Lopez J, Burchfield J, Blair D, Mele K, Ng Y, Vallotton P, et al. Identification of a distal GLUT4 trafficking event controlled by actin polymerization. Mol Biol Cell. 2009;20:3918-29 pubmed publisher
    The insulin-stimulated trafficking of GLUT4 to the plasma membrane in muscle and fat tissue constitutes a central process in blood glucose homeostasis...
  6. Ueda S, Kitazawa S, Ishida K, Nishikawa Y, Matsui M, Matsumoto H, et al. Crucial role of the small GTPase Rac1 in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma. FASEB J. 2010;24:2254-61 pubmed publisher
    ..We then examined whether insulin-stimulated translocation of the facilitative glucose transporter GLUT4 from its storage sites to the skeletal muscle sarcolemma depends on Rac1...
  7. Minokoshi Y, Kahn C, Kahn B. Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J Biol Chem. 2003;278:33609-12 pubmed
  8. Chen Y, Wang Y, Zhang J, Deng Y, Jiang L, Song E, et al. Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytes. J Cell Biol. 2012;198:545-60 pubmed publisher
    Rab proteins are important regulators of insulin-stimulated GLUT4 translocation to the plasma membrane (PM), but the precise steps in GLUT4 trafficking modulated by particular Rab proteins remain unclear...
  9. Shi J, Kandror K. The luminal Vps10p domain of sortilin plays the predominant role in targeting to insulin-responsive Glut4-containing vesicles. J Biol Chem. 2007;282:9008-16 pubmed
    In fat and skeletal muscle cells, insulin-responsive vesicles, or IRVs, deliver glucose transporter Glut4 and several associated proteins to the plasma membrane in response to hormonal stimulation...
  10. Roach W, Chavez J, Miinea C, Lienhard G. Substrate specificity and effect on GLUT4 translocation of the Rab GTPase-activating protein Tbc1d1. Biochem J. 2007;403:353-8 pubmed
    Insulin stimulation of the trafficking of the glucose transporter GLUT4 to the plasma membrane is controlled in part by the phosphorylation of the Rab GAP (GTPase-activating protein) AS160 (also known as Tbc1d4)...
  11. Komori T, Morikawa Y, Tamura S, Doi A, Nanjo K, Senba E. Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions. Brain Res. 2005;1049:34-42 pubmed
    ..Although GLUT4 is abundant in the hypothalamus as well as in these peripheral tissues, little is known about the role of GLUT4 in ..
  12. Nedachi T, Fujita H, Kanzaki M. Contractile C2C12 myotube model for studying exercise-inducible responses in skeletal muscle. Am J Physiol Endocrinol Metab. 2008;295:E1191-204 pubmed publisher
    ..and is also responsible for maintaining healthy muscle displaying enhanced insulin-responsive glucose uptake via GLUT4 translocation...
  13. Lauritzen H, Galbo H, Brandauer J, Goodyear L, Ploug T. Large GLUT4 vesicles are stationary while locally and reversibly depleted during transient insulin stimulation of skeletal muscle of living mice: imaging analysis of GLUT4-enhanced green fluorescent protein vesicle dynamics. Diabetes. 2008;57:315-24 pubmed
    Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules...
  14. Zisman A, Peroni O, Abel E, Michael M, Mauvais Jarvis F, Lowell B, et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med. 2000;6:924-8 pubmed
    ..4), which is expressed mainly in skeletal muscle, heart and adipose tissue. GLUT4 mediates glucose transport stimulated by insulin and contraction/exercise...
  15. Randhawa V, Ishikura S, Talior Volodarsky I, Cheng A, Patel N, Hartwig J, et al. GLUT4 vesicle recruitment and fusion are differentially regulated by Rac, AS160, and Rab8A in muscle cells. J Biol Chem. 2008;283:27208-19 pubmed publisher
    Insulin increases glucose uptake into muscle by enhancing the surface recycling of GLUT4 transporters. In myoblasts, insulin signals bifurcate downstream of phosphatidylinositol 3-kinase into separate Akt and Rac/actin arms...
  16. Shigematsu S, Watson R, Khan A, Pessin J. The adipocyte plasma membrane caveolin functional/structural organization is necessary for the efficient endocytosis of GLUT4. J Biol Chem. 2003;278:10683-90 pubmed
    ..well established that insulin stimulation of glucose uptake requires the translocation of intracellular localized GLUT4 protein to the cell surface membrane...
  17. Carvalho E, Kotani K, Peroni O, Kahn B. Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. Am J Physiol Endocrinol Metab. 2005;289:E551-61 pubmed
    ..In obesity and type 2 diabetes, glucose transporter 4 (GLUT4) is downregulated in adipose tissue, and glucose transport is also impaired in muscle...
  18. Zhao P, Yang L, Lopez J, Fan J, Burchfield J, Bai L, et al. Variations in the requirement for v-SNAREs in GLUT4 trafficking in adipocytes. J Cell Sci. 2009;122:3472-80 pubmed publisher
    ..In the present study we investigated the function and plasticity of v-SNAREs in insulin-regulated GLUT4 trafficking in adipocytes...
  19. Fujita H, Hatakeyama H, Watanabe T, Sato M, Higuchi H, Kanzaki M. Identification of three distinct functional sites of insulin-mediated GLUT4 trafficking in adipocytes using quantitative single molecule imaging. Mol Biol Cell. 2010;21:2721-31 pubmed publisher
    Insulin stimulation of glucose uptake is achieved by redistribution of insulin-responsive glucose transporters, GLUT4, from intracellular storage compartment(s) to the plasma membrane in adipocytes and muscle cells...
  20. Li L, Bakirtzi K, Watson R, Pessin J, Kandror K. The C-terminus of GLUT4 targets the transporter to the perinuclear compartment but not to the insulin-responsive vesicles. Biochem J. 2009;419:105-12, 1 p following 112 pubmed publisher
    Postprandial blood glucose clearance is mediated by GLUT4 (glucose transporter 4) which is translocated from an intracellular storage pool to the plasma membrane in response to insulin...
  21. Bogan J, Rubin B, Yu C, Löffler M, Orme C, Belman J, et al. Endoproteolytic cleavage of TUG protein regulates GLUT4 glucose transporter translocation. J Biol Chem. 2012;287:23932-47 pubmed publisher
    To promote glucose uptake into fat and muscle cells, insulin causes the translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface...
  22. Rossetti L, Stenbit A, Chen W, Hu M, Barzilai N, Katz E, et al. Peripheral but not hepatic insulin resistance in mice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene. J Clin Invest. 1997;100:1831-9 pubmed
    Glucose transporter type 4 (GLUT4) is insulin responsive and is expressed in striated muscle and adipose tissue...
  23. Kim J, Kandror K. The first luminal loop confers insulin responsiveness to glucose transporter 4. Mol Biol Cell. 2012;23:910-7 pubmed publisher
    Glucose transporter isoform 4 (GLUT4), is the sole glucose transporter responsible for the effect of insulin on postprandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown...
  24. Stöckli J, Davey J, Hohnen Behrens C, Xu A, James D, Ramm G. Regulation of glucose transporter 4 translocation by the Rab guanosine triphosphatase-activating protein AS160/TBC1D4: role of phosphorylation and membrane association. Mol Endocrinol. 2008;22:2703-15 pubmed publisher
    Insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane in muscle and fat cells depends on the phosphatidylinositide 3-kinase/Akt pathway...
  25. Abel E, Kaulbach H, Tian R, Hopkins J, Duffy J, Doetschman T, et al. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest. 1999;104:1703-14 pubmed
    Glucose enters the heart via GLUT1 and GLUT4 glucose transporters. GLUT4-deficient mice develop striking cardiac hypertrophy and die prematurely...
  26. Martin O, Lee A, McGraw T. GLUT4 distribution between the plasma membrane and the intracellular compartments is maintained by an insulin-modulated bipartite dynamic mechanism. J Biol Chem. 2006;281:484-90 pubmed
    The GLUT4 glucose transporter is predominantly retained inside basal fat and muscle cells, and it is rapidly recruited to the plasma membrane with insulin stimulation. There is controversy regarding the mechanism of basal GLUT4 retention...
  27. Knight J, Eyster C, Griesel B, Olson A. Regulation of the human GLUT4 gene promoter: interaction between a transcriptional activator and myocyte enhancer factor 2A. Proc Natl Acad Sci U S A. 2003;100:14725-30 pubmed
    The GLUT4 gene is subject to complex tissue-specific and metabolic regulation, with a profound impact on insulin-mediated glucose disposal...
  28. Liu L, Omata W, Kojima I, Shibata H. The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting to the insulin-responsive storage compartment in 3T3-L1 adipocytes. Diabetes. 2007;56:1977-85 pubmed
    The small ubiquitin-related modifier (SUMO) conjugating enzyme Ubc9 has been shown to upregulate GLUT4 in L6 myoblast cells, although the mechanism of action has remained undefined...
  29. Lodhi I, Chiang S, Chang L, Vollenweider D, Watson R, Inoue M, et al. Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4 trafficking in adipocytes. Cell Metab. 2007;5:59-72 pubmed
    Insulin stimulates glucose uptake by promoting translocation of the Glut4 glucose transporter from intracellular storage compartments to the plasma membrane...
  30. Sadacca L, Bruno J, Wen J, Xiong W, McGraw T. Specialized sorting of GLUT4 and its recruitment to the cell surface are independently regulated by distinct Rabs. Mol Biol Cell. 2013;24:2544-57 pubmed publisher
    ..glucose homeostasis: stimulation of adipocytes with insulin results in insertion of the glucose transporter GLUT4 into the plasma membrane and subsequent glucose uptake...
  31. Huang S, Lifshitz L, Jones C, Bellve K, Standley C, Fonseca S, et al. Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranes. Mol Cell Biol. 2007;27:3456-69 pubmed
    ..reveals highly mobile structures containing enhanced green fluorescent protein-tagged glucose transporter 4 (GLUT4) within a zone about 100 nm beneath the plasma membrane of 3T3-L1 adipocytes...
  32. Hosaka T, Brooks C, Presman E, Kim S, Zhang Z, Breen M, et al. p115 Interacts with the GLUT4 vesicle protein, IRAP, and plays a critical role in insulin-stimulated GLUT4 translocation. Mol Biol Cell. 2005;16:2882-90 pubmed
    Insulin-regulated aminopeptidase (IRAP) is an abundant cargo protein of Glut4 storage vesicles (GSVs) that traffics to and from the plasma membrane in response to insulin...
  33. Xu Y, Rubin B, Orme C, Karpikov A, Yu C, Bogan J, et al. Dual-mode of insulin action controls GLUT4 vesicle exocytosis. J Cell Biol. 2011;193:643-53 pubmed publisher
    Insulin stimulates translocation of GLUT4 storage vesicles (GSVs) to the surface of adipocytes, but precisely where insulin acts is controversial...
  34. Bai L, Wang Y, Fan J, Chen Y, Ji W, Qu A, et al. Dissecting multiple steps of GLUT4 trafficking and identifying the sites of insulin action. Cell Metab. 2007;5:47-57 pubmed
    Insulin-stimulated GLUT4 translocation is central to glucose homeostasis...
  35. Blot V, McGraw T. GLUT4 is internalized by a cholesterol-dependent nystatin-sensitive mechanism inhibited by insulin. EMBO J. 2006;25:5648-58 pubmed
    Insulin slows GLUT4 internalization by an unknown mechanism. Here we show that in unstimulated adipocytes, GLUT4 is internalized by two mechanisms...
  36. Lizunov V, Lisinski I, Stenkula K, Zimmerberg J, Cushman S. Insulin regulates fusion of GLUT4 vesicles independent of Exo70-mediated tethering. J Biol Chem. 2009;284:7914-9 pubmed publisher
    Insulin regulates cellular glucose uptake by changing the amount of glucose transporter-4 (GLUT4) in the plasma membrane through stimulation of GLUT4 exocytosis...
  37. Jiang H, Li J, Katz E, Charron M. GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane. Biochem Biophys Res Commun. 2001;284:519-25 pubmed
    ..Insulin elicits increased glucose uptake by recruiting GLUT4 from a specialized intracellular storage site to the cell surface...
  38. Sajan M, Bandyopadhyay G, Kanoh Y, Standaert M, Quon M, Reed B, et al. Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D. Biochem J. 2002;362:665-74 pubmed
    Sorbitol, "osmotic stress", stimulates GLUT4 glucose transporter translocation to the plasma membrane and glucose transport by a phosphatidylinositol (PI) 3-kinase-independent mechanism that reportedly involves non-receptor ..
  39. Gonzalez E, Flier E, Molle D, Accili D, McGraw T. Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor. Proc Natl Acad Sci U S A. 2011;108:10162-7 pubmed publisher
    ..of chronic hyperinsulinemia that adipocytes develop selective insulin resistance in which translocation of the GLUT4 glucose transporter to the cell surface is blunted yet nuclear exclusion of the FoxO1 transcription factor is ..
  40. Larance M, Ramm G, St ckli J, van Dam E, Winata S, Wasinger V, et al. Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking. J Biol Chem. 2005;280:37803-13 pubmed publisher
    Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane...
  41. Fueger P, Hess H, Posey K, Bracy D, Pencek R, Charron M, et al. Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on glucose phosphorylation capacity in the conscious mouse. J Biol Chem. 2004;279:50956-61 pubmed
    Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU...
  42. Carvalho E, Schellhorn S, Zabolotny J, Martin S, Tozzo E, Peroni O, et al. GLUT4 overexpression or deficiency in adipocytes of transgenic mice alters the composition of GLUT4 vesicles and the subcellular localization of GLUT4 and insulin-responsive aminopeptidase. J Biol Chem. 2004;279:21598-605 pubmed
    The majority of GLUT4 is sequestered in unique intracellular vesicles in the absence of insulin. Upon insulin stimulation GLUT4 vesicles translocate to, and fuse with, the plasma membrane...
  43. Jedrychowski M, Gartner C, Gygi S, Zhou L, Herz J, Kandror K, et al. Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling. J Biol Chem. 2010;285:104-14 pubmed publisher
    Insulin stimulates the translocation of intracellular GLUT4 to the plasma membrane where it functions in adipose and muscle tissue to clear glucose from circulation...
  44. Semiz S, Park J, Nicoloro S, Furcinitti P, Zhang C, Chawla A, et al. Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules. EMBO J. 2003;22:2387-99 pubmed
    ..stimulates glucose uptake in muscle and adipose cells by mobilizing intracellular membrane vesicles containing GLUT4 glucose transporter proteins to the plasma membrane...
  45. Brissova M, Blaha M, Spear C, Nicholson W, Radhika A, Shiota M, et al. Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. Am J Physiol Endocrinol Metab. 2005;288:E707-14 pubmed
    ..mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (..
  46. Macaulay S, Grusovin J, Stoichevska V, Ryan J, Castelli L, Ward C. Cellular munc18c levels can modulate glucose transport rate and GLUT4 translocation in 3T3L1 cells. FEBS Lett. 2002;528:154-60 pubmed
    Munc18c has been shown to bind syntaxin 4 and to play a role in GLUT4 translocation and glucose transport, although this role is as yet poorly defined...
  47. Xiong W, Jordens I, Gonzalez E, McGraw T. GLUT4 is sorted to vesicles whose accumulation beneath and insertion into the plasma membrane are differentially regulated by insulin and selectively affected by insulin resistance. Mol Biol Cell. 2010;21:1375-86 pubmed publisher
    Insulin stimulates glucose transport by recruiting the GLUT4 glucose transporter to the plasma membrane...
  48. Morris N, Ross S, Lane W, Moestrup S, Petersen C, Keller S, et al. Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes. J Biol Chem. 1998;273:3582-7 pubmed
    Vesicles containing the glucose transporter GLUT4 from rat adipocytes contain a major protein of 110 kDa. We have isolated this protein, obtained the sequences of peptides, and cloned a large portion of its cDNA...
  49. Ramm G, Larance M, Guilhaus M, James D. A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. J Biol Chem. 2006;281:29174-80 pubmed
    Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway...
  50. Brewer P, Romenskaia I, Kanow M, Mastick C. Loss of AS160 Akt substrate causes Glut4 protein to accumulate in compartments that are primed for fusion in basal adipocytes. J Biol Chem. 2011;286:26287-97 pubmed publisher
    The Akt substrate AS160 (TCB1D4) regulates Glut4 exocytosis; shRNA knockdown of AS160 increases surface Glut4 in basal adipocytes...
  51. Shi X, Burkart A, Nicoloro S, Czech M, Straubhaar J, Corvera S. Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells. J Biol Chem. 2008;283:30658-67 pubmed publisher
    ..However, insulin-stimulated GLUT4 translocation to the cell surface and subsequent glucose transport are impaired in Tfam knockdown cells...
  52. Yoshizaki T, Imamura T, Babendure J, Lu J, Sonoda N, Olefsky J. Myosin 5a is an insulin-stimulated Akt2 (protein kinase Bbeta) substrate modulating GLUT4 vesicle translocation. Mol Cell Biol. 2007;27:5172-83 pubmed
    Phosphatidylinositol 3-kinase activation of Akt signaling is critical to insulin-stimulated glucose transport and GLUT4 translocation...
  53. Fueger P, Li C, Ayala J, Shearer J, Bracy D, Charron M, et al. Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. J Physiol. 2007;582:801-12 pubmed
    The absence of GLUT4 severely impairs basal glucose uptake in vivo, but does not alter glucose homeostasis or circulating insulin...
  54. Abel E, Peroni O, Kim J, Kim Y, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409:729-33 pubmed
    ..The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage ..
  55. Williams D, Pessin J. Mapping of R-SNARE function at distinct intracellular GLUT4 trafficking steps in adipocytes. J Cell Biol. 2008;180:375-87 pubmed publisher
    ..R-SNAREs, we have taken advantage of the temporal requirements of adipocyte biosynthetic sorting of a dual-tagged GLUT4 reporter (myc-GLUT4-GFP) coupled with small interfering RNA gene silencing...
  56. Stenbit A, Katz E, Chatham J, Geenen D, Factor S, Weiss R, et al. Preservation of glucose metabolism in hypertrophic GLUT4-null hearts. Am J Physiol Heart Circ Physiol. 2000;279:H313-8 pubmed
    b>GLUT4-null mice lacking the insulin-sensitive glucose transporter are not diabetic but do exhibit abnormalities in glucose and lipid metabolism. The most striking morphological consequence of ablating GLUT4 is cardiac hypertrophy...
  57. Blot V, McGraw T. Molecular mechanisms controlling GLUT4 intracellular retention. Mol Biol Cell. 2008;19:3477-87 pubmed publisher
    In basal adipocytes, glucose transporter 4 (GLUT4) is sequestered intracellularly by an insulin-reversible retention mechanism...
  58. Charron M, Katz E, Olson A. GLUT4 gene regulation and manipulation. J Biol Chem. 1999;274:3253-6 pubmed
  59. Funaki M, Randhawa P, Janmey P. Separation of insulin signaling into distinct GLUT4 translocation and activation steps. Mol Cell Biol. 2004;24:7567-77 pubmed
    b>GLUT4 (glucose transporter 4) plays a pivotal role in insulin-induced glucose uptake to maintain normal blood glucose levels...
  60. Xie X, Gong Z, Mansuy Aubert V, Zhou Q, Tatulian S, Sehrt D, et al. C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. Cell Metab. 2011;14:378-89 pubmed publisher
    ..Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM)...
  61. Kanda H, Tamori Y, Shinoda H, Yoshikawa M, Sakaue M, Udagawa J, et al. Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization. J Clin Invest. 2005;115:291-301 pubmed
    ..glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the subsequent fusion of these vesicles with the plasma ..
  62. Yeh T, Sbodio J, Tsun Z, Luo B, Chi N. Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. Biochem J. 2007;402:279-90 pubmed
    The glucose transporter GLUT4 and the aminopeptidase IRAP (insulin-responsive aminopeptidase) are the major cargo proteins of GSVs (GLUT4 storage vesicles) in adipocytes and myocytes...
  63. Bose A, Guilherme A, Robida S, Nicoloro S, Zhou Q, Jiang Z, et al. Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c. Nature. 2002;420:821-4 pubmed
    Insulin stimulates glucose uptake in muscle and adipocytes by signalling the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface...
  64. Khan A, Capilla E, Hou J, Watson R, Smith J, Pessin J. Entry of newly synthesized GLUT4 into the insulin-responsive storage compartment is dependent upon both the amino terminus and the large cytoplasmic loop. J Biol Chem. 2004;279:37505-11 pubmed
    We have recently reported that following initial biosynthesis, the GLUT4 protein exits the Golgi apparatus and directly enters the insulin-responsive compartment(s) without transiting the plasma membrane...
  65. Sano H, Roach W, Peck G, Fukuda M, Lienhard G. Rab10 in insulin-stimulated GLUT4 translocation. Biochem J. 2008;411:89-95 pubmed
    In fat and muscle cells, insulin stimulates the movement to and fusion of intracellular vesicles containing GLUT4 with the plasma membrane, a process referred to as GLUT4 translocation...
  66. Kaestner K, Christy R, Lane M. Mouse insulin-responsive glucose transporter gene: characterization of the gene and trans-activation by the CCAAT/enhancer binding protein. Proc Natl Acad Sci U S A. 1990;87:251-5 pubmed
    ..Here we report the isolation and characterization of the corresponding mouse gene designated GLUT4. The GLUT4 gene spans 7 kilobases and consists of 11 exons and 10 introns...
  67. Kane S, Lienhard G. Calmodulin binds to the Rab GTPase activating protein required for insulin-stimulated GLUT4 translocation. Biochem Biophys Res Commun. 2005;335:175-80 pubmed
    ..Phosphorylation of AS160 in adipocytes is required for insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane...
  68. Liao W, Nguyen M, Imamura T, Singer O, Verma I, Olefsky J. Lentiviral short hairpin ribonucleic acid-mediated knockdown of GLUT4 in 3T3-L1 adipocytes. Endocrinology. 2006;147:2245-52 pubmed
    ..We chose to target GLUT4 to validate this approach...
  69. Inoue M, Chang L, Hwang J, Chiang S, Saltiel A. The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin. Nature. 2003;422:629-33 pubmed
    Insulin stimulates glucose transport by promoting exocytosis of the glucose transporter Glut4 (refs 1, 2)...
  70. Katz E, Stenbit A, Hatton K, Depinho R, Charron M. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature. 1995;377:151-5 pubmed
    The insulin-sensitive glucose transporter, GLUT4, is the most abundant facilitative glucose transporter in muscle and adipose tissue, the major sites for postprandial glucose disposal...
  71. Hansen P, Gulve E, Marshall B, Gao J, Pessin J, Holloszy J, et al. Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice overexpressing the Glut4 glucose transporter. J Biol Chem. 1995;270:1679-84 pubmed
    Skeletal muscle glucose transport and metabolism were studied in a line of transgenic mice overexpressing the human Glut4 facilitative glucose transporter...
  72. Gross D, Farmer S, Pilch P. Glut4 storage vesicles without Glut4: transcriptional regulation of insulin-dependent vesicular traffic. Mol Cell Biol. 2004;24:7151-62 pubmed
    ..glucose uptake in the NIH-PPAR gamma cells is their virtual lack of the insulin-responsive glucose transporter, Glut4. The NIH-PPAR gamma cells express functionally active components of the insulin receptor-signaling pathway (the ..
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    Insulin-stimulated GLUT4 translocation to the plasma membrane constitutes a key process for blood glucose control...
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    b>GLUT4 trafficking to the plasma membrane of muscle and fat cells is regulated by insulin. An important component of insulin-regulated GLUT4 distribution is the Akt substrate AS160 rab GTPase-activating protein...
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    ..muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution...
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    Insulin stimulates the rapid translocation of intracellular glucose transporters of the GLUT4 isotype to the plasma membrane in fat and muscle cells...
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    The ability of muscles from Glut 4-null mice to take up and metabolize glucose has been studied in the isolated white EDL and red soleus muscles...
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    The insulin-responsive glucose transporter GLUT4 plays an essential role in glucose homeostasis. A novel assay was used to study GLUT4 trafficking in 3T3-L1 fibroblasts/preadipocytes and adipocytes...
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    The Glut4 glucose transporter undergoes complex insulin-regulated subcellular trafficking in adipocytes...
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    Expression of GLUT4 in fast-twitch skeletal muscle fibers of GLUT4 null mice (G4-MO) normalized glucose uptake in muscle and restored peripheral insulin sensitivity...
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    ..hypertrophy observed in mice with cardiac specific ablation of the insulin sensitive glucose transporter 4 gene (GLUT4, G4H(-/-) )...
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    Insulin-stimulated translocation of the glucose transporter GLUT4 to the cell surface in fat and muscle cells is the basis for insulin-stimulated glucose transport...
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    A new mouse model has been developed to study the localisation and trafficking of the glucose transporter GLUT4 in muscle...
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    ..The glucose transporter type-4 (GLUT4) is primarily responsible for the insulin-stimulated increase in glucose uptake...