Open Access Articles- Top Results for GLUT4


SymbolsSLC2A4 ; GLUT4
External IDsOMIM138190 MGI95758 HomoloGene74381 IUPHAR: 878 ChEMBL: 5874 GeneCards: SLC2A4 Gene
RNA expression pattern
File:PBB GE SLC2A4 206603 at tn.png
More reference expression data
RefSeq (mRNA)NM_001042NM_009204
RefSeq (protein)NP_001033NP_033230
Location (UCSC)Chr 17:
7.18 – 7.19 Mb
Chr 11:
69.94 – 69.95 Mb
PubMed search[1][2]

Glucose transporter type 4, also known as GLUT4, is a protein that in humans is encoded by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle (skeletal and cardiac). The first evidence for this distinct glucose transport protein was provided by David James in 1988.[1] The gene that encodes GLUT4 was cloned[2][3] and mapped in 1989.[4]

Recent reports demonstrated the presence of GLUT4 gene in central nervous system such as the hippocampus. Moreover, impairment in insulin-stimulated trafficking of GLUT4 in the hippocampus result in decreased metabolic activities and plasticity of hippocampal neurons, which leads to depressive like behaviour and cognitive dysfunction.[5][6][7]

Tissue distribution

GLUT4 is primarily found in:



Under conditions of low insulin, GLUT4 is sequestered in intracellular vesicles in muscle and fat cells. Insulin induces a rapid increase in the uptake of glucose by inducing the translocation of GLUT4 from these vesicles to the plasma membrane. As the vesicles fuse with the plasma membrane, GLUT4 transporters are inserted and become available for transporting glucose, and glucose absorption increases.[8]

Insulin binds to the insulin receptor in its dimeric form and activates the receptor's tyrosine-kinase domain. The receptor then phosphorylates and subsequently recruits Insulin Receptor Substrate or IRS-1, which in turn binds the enzyme PI-3 kinase through the binding of the enzyme's SH2 domain to the pTyr of IRS. PI-3 kinase converts the membrane lipid PIP2 to PIP3. PIP3 is specifically recognized by the PH domains of PKB (protein kinase B)or AKT, and also for PDK1 which, being localized together with PKB, can phosphorylate and activate PKB. Once phosphorylated, PKB is in its active form and phosphorylates TBC1D4, which inhibits the GAP domain or the GTPase-activating domain associated with TBC1D4, allowing for Rab protein to change from its GDP to GTP bound state. Inhibition of the GTPase-activating domain leaves proteins next in the cascade in their active form and stimulates GLUT4 to be expressed on the plasma membrane.

At the cell surface, GLUT4 permits the facilitated diffusion of circulating glucose down its concentration gradient into muscle and fat cells. Once within cells, glucose is rapidly phosphorylated by glucokinase in the liver and hexokinase in other tissues to form glucose-6-phosphate, which then enters glycolysis or is polymerized into glycogen. Glucose-6-phosphate cannot diffuse back out of cells, which also serves to maintain the concentration gradient for glucose to passively enter cells.[9]

Knockout mice that are heterozygous for GLUT4 develop insulin resistance in their muscles as well as diabetes.[10]

Muscle contraction

Muscle contraction stimulates muscle cells to translocate GLUT4 receptors to their surfaces. This is especially true in cardiac muscle, where continuous contraction can be relied upon; but is observed to a lesser extent in skeletal muscle.[11]


GLUT4 has been shown to interact with death-associated protein 6.[12]

Interactive pathway map

Template:GlycolysisGluconeogenesis WP534


  1. ^ James DE, Brown R, Navarro J, Pilch PF (May 1988). "Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein". Nature 333 (6169): 183–5. PMID 3285221. doi:10.1038/333183a0. 
  2. ^ James DE, Strube M, Mueckler M (March 1989). "Molecular cloning and characterization of an insulin-regulatable glucose transporter". Nature 338 (6210): 83–7. PMID 2645527. doi:10.1038/338083a0. 
  3. ^ Birnbaum MJ (April 1989). "Identification of a novel gene encoding an insulin-responsive glucose transporter protein". Cell 57 (2): 305–15. PMID 2649253. doi:10.1016/0092-8674(89)90968-9. 
  4. ^ Bell GI, Murray JC, Nakamura Y, Kayano T, Eddy RL, Fan YS, Byers MG, Shows TB (August 1989). "Polymorphic human insulin-responsive glucose-transporter gene on chromosome 17p13". Diabetes 38 (8): 1072–5. PMID 2568955. doi:10.2337/diabetes.38.8.1072. 
  5. ^ Patel, Sita Sharan; Udayabanu (March 2014). "Malairaman". Metab Brain Dis 29 (1): 121–30. PMID 24435938. doi:10.1007/s11011-014-9480-0. 
  6. ^ Piroli, GG; Grillo, CA; Reznikov, LR; Adams, S; McEwen, BS; Charron, MJ; Reagan, LP (2007). "Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus.". Neuroendocrinology 85 (2): 71–80. PMID 17426391. doi:10.1159/000101694. 
  7. ^ Huang CC, Lee CC, Hsu KS (2010). "The role of insulin receptor signaling in synaptic plasticity and cognitive function". Chang Gung Med J 33 (2): 115–25. PMID 20438663. 
  8. ^ Cushman SW, Wardzala LJ (May 1980). "Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane" (PDF). J. Biol. Chem. 255 (10): 4758–62. PMID 6989818. 
  9. ^ Watson RT, Kanzaki M, Pessin JE (2004). "Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes". Endocr. Rev. 25 (2): 177–204. PMID 15082519. doi:10.1210/er.2003-0011. 
  10. ^ Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, Factor SM, Houseknecht K, Katz EB, Charron MJ (1997). "GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes". Nature Medicine 3 (10): 1096–1101. PMID 9334720. doi:10.1038/nm1097-1096. 
  11. ^ Lund S, Holman GD, Schmitz O, Pedersen O (1995). "Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin". Proc. Natl. Acad. Sci. U.S.A. 92 (13): 5817–21. PMC 41592. PMID 7597034. doi:10.1073/pnas.92.13.5817. 
  12. ^ Lalioti VS, Vergarajauregui S, Pulido D, Sandoval IV (May 2002). "The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. This can also bind to lipoproteins for transport. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1". J. Biol. Chem. 277 (22): 19783–91. PMID 11842083. doi:10.1074/jbc.M110294200. 

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