View source for GLUT1

{{Short description|Uniporter protein}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox_gene}}
'''Glucose transporter 1''' (or '''GLUT1'''), also known as '''solute carrier family 2, facilitated glucose transporter member 1''' (SLC2A1), is a [[uniporter]] [[protein]] that in humans is encoded by the ''SLC2A1'' [[gene]].<ref name="pmid3839598">{{cite journal | vauthors = Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF | title = Sequence and structure of a human glucose transporter | journal = Science | volume = 229 | issue = 4717 | pages = 941–5 | date = September 1985 | pmid = 3839598 | doi = 10.1126/science.3839598 | bibcode = 1985Sci...229..941M }}</ref> GLUT1 [[facilitated diffusion|facilitates]] the transport of [[glucose]] across the [[cell membrane|plasma membranes]] of mammalian cells.<ref name="pmid8839927">{{cite journal | vauthors = Olson AL, Pessin JE | title = Structure, function, and regulation of the mammalian facilitative glucose transporter gene family | journal = Annual Review of Nutrition | volume = 16 | pages = 235–56 | year = 1996 | pmid = 8839927 | doi = 10.1146/annurev.nu.16.070196.001315 }}</ref>  This gene encodes a facilitative [[glucose transporter]] that is highly expressed in erythrocytes and endothelial cells, including cells of the [[blood–brain barrier]]. The encoded protein is found primarily in the [[cell membrane]] and on the cell surface, where it can also function as a [[Cell surface receptor|receptor]] for [[Human T-lymphotropic virus|human T-cell leukemia virus (HTLV)]] [[Human T-lymphotropic virus 1|I]] and [[Human T-lymphotropic virus 2|II]].<ref name="entrez">{{citation-attribution|1={{cite web|url=https://www.ncbi.nlm.nih.gov/gene/54968|title=Entrez Gene: Transmembrane protein 70|access-date=2018-08-14}}}}</ref> GLUT1 accounts for 2 percent of the protein in the plasma membrane of erythrocytes.  During early development, GLUT1 expression is compartmentalized across different tissues, ensuring that metabolic requirements are met in a tissue-specific manner. This tissue-specific glucose metabolism is essential for regulating the differentiation of specific lineages, such as the epiblast to mesoderm transition during gastrulation. GLUT1's role in glucose uptake supports localized metabolic needs that interact with developmental signalling pathways to shape the emerging body plan.<ref name=dc>{{cite journal | vauthors = Cao D, Bergmann J, Zhong L, Hemalatha A, Dingare C, Jensen T, Cox AL, Greco V, Steventon B, Sozen B | title = Selective utilization of glucose metabolism guides mammalian gastrulation | journal = Nature | volume = 634 | issue = 8035 | pages = 919–928 | date = October 2024 | pmid = 39415005 | pmc = 11499262 | doi = 10.1038/s41586-024-08044-1 | bibcode = 2024Natur.634..919C }}</ref> 

[[Mutation]]s in this gene can cause [[Glut1 deficiency|GLUT1 deficiency syndrome 1, GLUT1 deficiency syndrome 2]], [[idiopathic generalized epilepsy]] 12, [[dystonia]] 9, and [[Hereditary stomatocytosis#Variants|stomatin-deficient cryohydrocytosis]].<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/P11166|title=SLC2A1 – Solute carrier family 2, facilitated glucose transporter member 1 – Homo sapiens (Human) – SLC2A1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-27}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}</ref> Disruption in GLUT1-mediated glucose transport can lead to defects in cell differentiation and morphogenesis.

== Discovery ==

GLUT1 was the first [[glucose transporter]] to be characterized. GLUT1 is highly conserved.<ref name="pmid3839598"/> GLUT1 of humans and mice have 98% identity at the amino acid level. GLUT1 is encoded by the SLC2 gene and is one of a family of 14 genes encoding GLUT proteins.<ref>{{cite journal | vauthors = Mueckler M, Thorens B | title = The SLC2 (GLUT) family of membrane transporters | journal = Molecular Aspects of Medicine | volume = 34 | issue = 2–3 | pages = 121–38 | year = 2013 | pmid = 23506862 | pmc = 4104978 | doi = 10.1016/j.mam.2012.07.001 }}</ref>

== Structure ==

The ''SLC2A1'' gene is located on the p arm of [[chromosome 1]] in position 34.2 and has 10 [[exon]]s spanning 33,802 base pairs.<ref name = "entrez"/> The gene produces a 54.1 kDa protein composed of 492 [[amino acids]].<ref name=COPaKB>{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/P11166 | website = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = SLC2A1 – Solute carrier family 2, facilitated glucose transporter member 1 }}</ref><ref>{{cite journal | vauthors = Wang D, Kranz-Eble P, De Vivo DC | title = Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome | journal = Human Mutation | volume = 16 | issue = 3 | pages = 224–31 | date = September 2000 | pmid = 10980529 | doi = 10.1002/1098-1004(200009)16:3<224::AID-HUMU5>3.0.CO;2-P | s2cid = 3169748 | doi-access = free }}</ref><ref name=":1">Online Mendelian Inheritance in Man. Johns Hopkins University, Baltimore, MD. MIM Number: {138140}: {08/21/2017}: . World Wide Web URL: https://omim.org/entry/138140?search=138140&highlight=138140</ref> It is a [[Integral membrane protein#Integral polytopic protein|multi-pass protein]] located in the cell membrane.<ref name=":0" /><ref name=":3" /> This protein lacks a [[Signal peptide|signal sequence]]; its [[C-terminus]], [[N-terminus]], and the very [[Hydrophile|hydrophilic]] [[protein domain|domain]] in the protein's center are all predicted to lie on the [[cytoplasm]]ic side of the cell membrane.<ref name=":1" /><ref name="pmid3839598"/>

GLUT1 behaves as a [[Michaelis–Menten]] enzyme and contains 12 membrane-spanning [[alpha helices]], each containing 20 amino acid residues. A helical wheel analysis shows that the membrane-spanning alpha-helices are [[amphipathic]], with one side being polar and the other side hydrophobic. Six of these membrane-spanning helices are believed to bind together in the membrane to create a polar channel in the center through which glucose can traverse, with the hydrophobic regions on the outside of the channel adjacent to the fatty acid tails of the membrane.{{citation needed|date=November 2015}}

== Function ==

Energy-yielding metabolism in [[erythrocytes]] depends on a constant supply of glucose from the [[blood plasma]], where the glucose concentration is maintained at about 5mM. Glucose enters the erythrocyte by [[facilitated diffusion]] via a specific glucose transporter, at a rate of about 50,000 times greater than uncatalyzed transmembrane diffusion. The glucose transporter of erythrocytes (called GLUT1 to distinguish it from related glucose transporters in other tissues) is a type III [[integral protein]] with 12 hydrophobic segments, each of which is believed to form a membrane-spanning [[Alpha helix|helix]]. The detailed structure of GLUT1 is not known yet, but one plausible model suggests that the side-by-side assembly of several helices produces a transmembrane [[Ion channel|channel]] lined with hydrophilic residues that can hydrogen-bond with glucose as it moves through the channel.<ref name=Lehninger2008>{{cite book |vauthors=Nelson DL, Cox MM |year=2008 |title=Lehninger, Principles of Biochemistry |publisher=W. H. Freeman |isbn=978-0-7167-7108-1 |url-access=registration |url=https://archive.org/details/lehningerprincip00lehn_1}}</ref>

GLUT1 is responsible for the low level of basal glucose uptake required to sustain respiration in all cells. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels.<ref name=dc/>

GLUT1's function extends beyond its role in basic glucose transport, as it has been shown to interact with molecular signalling pathways during early embryogenesis. Specifically, it is involved in processes like mesodermal formation, neural tube development, and cell-fate transitions. It is also a key player in directing embryonic development, influencing cell fate transitions, and guiding tissue-specific differentiation during critical stages of embryogenesis. GLUT1-mediated glucose uptake plays a critical role in early embryogenesis, where glucose metabolism undergoes a conserved shift at the time of implantation. It helps fine-tune cell fate decisions and developmental transitions during this stage.<ref name=dc/>

Recent studies have shown that glucose metabolism actively directs cell fate. For example, the hexosamine biosynthetic pathway, which depends on glucose metabolism, produces UDP-GlcNAc,{{clarify|What do these letters mean?|date=April 2025}} a molecule crucial for cell differentiation and morphogenetic processes. This highlights how GLUT1-mediated glucose transport can influence signalling pathways such as ERK,{{clarify|What is ERK?|date=April 2025}} which are critical for the differentiation of epiblast cells into mesodermal tissue, guiding embryonic cell fate transitions. Influences cellular responses to key morphogens, such as FGF8 and FGF4, essential for proper development.<ref name=dc/>

GLUT1 is also a major receptor for uptake of [[vitamin C]] as well as [[glucose]], especially in non vitamin C producing mammals as part of an adaptation to compensate by participating in a Vitamin C recycling process.  In mammals that do produce Vitamin C, [[GLUT4]] is often expressed instead of GLUT1.<ref name="Amélie2008">{{cite journal | vauthors = Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N | title = Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C | journal = Cell | volume = 132 | issue = 6 | pages = 1039–48 | date = March 2008 | pmid = 18358815 | doi = 10.1016/j.cell.2008.01.042 | s2cid = 18128118 | doi-access = free }}*{{lay source |template = cite web|url = https://www.sciencedaily.com/releases/2008/03/080320120726.htm|title = How Humans Make Up For An 'Inborn' Vitamin C Deficiency|date = March 21, 2008 |website = ScienceDaily }}</ref>

===Role of metabolism in Gastrulation===

Gastrulation is a critical phase of embryogenesis where the primary body plan is established through the movement and differentiation of cells. Glucose uptake and utilization are compartmentalized across different embryonic tissues, with distinct waves of glucose activity in the epiblast and mesoderm during gastrulation.<ref name=dc/>

Spatiotemporal Waves of Glucose Uptake: Two waves of glucose uptake have been identified during mouse gastrulation. The first wave occurs in transitionary epiblast cells, located in the posterior region of the embryo. These cells exhibit an initial surge in glucose uptake, which expands as the primitive streak elongates. The second wave occurs in mesodermal cells, as they exit the primitive streak and migrate laterally to form mesenchymal tissue. This second wave of glucose activity coincides with increased metabolic demands during mesodermal migration and mesenchymal cell behavior. These waves of glucose uptake are  linked with ERK signaling, an important pathway regulating cellular behavior during development. The coupling of glucose metabolism with ERK activity suggests that metabolic signals not only provide energy but also act as regulators of developmental processes. This interaction is especially significant for mesoderm migration, as inhibition of glycolysis or ERK signaling disrupts proper mesodermal development.<ref name=dc/>

Another critical aspect of glucose metabolism during gastrulation is the hexosamine biosynthetic pathway, which plays a key role in preparing epiblast cells for entry into the primitive streak. The pathway is important for regulating cell-fate transitions in the epiblast, supporting the initiation of mesodermal formation. Inhibition of the hexosamine biosynthetic pathway results in delayed primitive streak development, highlighting its importance in early embryonic development.<ref name=dc/>

Glucose metabolism shifts significantly after implantation, with increased glucose uptake supporting cellular processes such as proliferation and differentiation. However, high glucose uptake does not always correlate with increased glycolytic activity, as glucose can also be directed into parallel metabolic pathways.<ref name=dc/>

Given the high level of glucose activity in epiblast cells before primitive streak entry, it was hypothesized that metabolic regulation could play a role in the epithelial-to-mesenchymal transition during mouse gastrulation. Transitionary epiblast cells showed weakened E-cadherin expression but exhibited GLUT1 and GLUT3 activity, indicating enhanced glucose uptake during early-stage epithelial-to-mesenchymal transition.<ref name=dc/>

Together, these findings demonstrate that hexosamine biosynthetic pathway is crucial for regulating epithelial-to-mesenchymal transition in the posterior epiblast during mouse gastrulation, facilitating both the mesodermal fate acquisition and the ingression of epiblast cells into the primitive streak. The anterior epiblast cells, in contrast, are influenced by the anterior visceral endoderm, which prevents posteriorization and inhibits epithelial-to-mesenchymal transition, allowing glucose metabolism to shift towards ectoderm fate at later stages.<ref name=dc/>

== Tissue distribution ==

GLUT1 expression occurs in almost all tissues, with the degree of expression typically correlating with the rate of cellular glucose metabolism. In the adult it is expressed at highest levels in [[erythrocytes]] and also in the [[endothelial]] cells of barrier tissues such as the [[blood–brain barrier]].<ref>{{cite journal | vauthors = Uldry M, Thorens B | title = The SLC2 family of facilitated hexose and polyol transporters | journal = Pflügers Archiv | volume = 447 | issue = 5 | pages = 480–9 | date = February 2004 | pmid = 12750891 | doi = 10.1007/s00424-003-1085-0 | s2cid = 25539725 | url = http://doc.rero.ch/record/316469/files/424_2004_Article_1264.pdf }}</ref>

== Clinical significance ==

Mutations in the GLUT1 gene are responsible for GLUT1 deficiency or [[De Vivo disease]], which is a rare [[Dominance (genetics)|autosomal dominant]] disorder.<ref>{{cite journal | vauthors = Seidner G, Alvarez MG, Yeh JI, O'Driscoll KR, Klepper J, Stump TS, Wang D, Spinner NB, Birnbaum MJ, De Vivo DC | title = GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood–brain barrier hexose carrier | journal = Nature Genetics | volume = 18 | issue = 2 | pages = 188–91 | date = February 1998 | pmid = 9462754 | doi = 10.1038/ng0298-188 | s2cid = 7378231 }}</ref> This disease is characterized by a low [[cerebrospinal fluid]] glucose concentration (hypoglycorrhachia), a type of [[neuroglycopenia]], which results from impaired glucose transport across the blood–brain barrier.

=== GLUT1 deficiency syndrome 1 ===
Many mutations in the ''SLC2A1'' gene, including LYS456TER, TYR449TER, LYS256VAL, ARG126HIS, ARG126LEU and GLY91ASP,  have been shown to cause GLUT1 deficiency syndrome 1 (GLUT1DS1), a [[Neurological disorder|neurologic disorder]] showing wide [[Phenotype|phenotypic]] variability. This disease can be inherited in either an [[Genetic disorder#Autosomal recessive|autosomal recessive]] or [[Genetic disorder#Autosomal dominant|autosomal dominant]] manner.<ref name=":1" /> The most severe 'classic' phenotype comprises infantile-onset [[Epileptic seizure|epileptic]] [[encephalopathy]] associated with [[Global developmental delay|delayed development]], acquired [[microcephaly]], [[Motor coordination|motor incoordination]], and [[spasticity]]. Onset of [[seizure]]s, usually characterized by [[apnea|apneic episodes]], [[staring]] spells, and episodic [[eye movements]], occurs within the first 4 months of life. Other [[Paroxysmal attack|paroxysmal]] findings include intermittent [[ataxia]], [[Confusion#Medical term|confusion]], [[lethargy]], [[sleep disorder|sleep disturbance]], and [[headache]]. Varying degrees of [[Cognitive deficit|cognitive impairment]] can occur, ranging from [[Learning disability|learning disabilities]] to severe [[Intellectual disability|mental retardation]].<ref name=":0" /><ref name=":3" />

=== GLUT1 deficiency syndrome 2 ===
Other mutations, like GLY314SER, ALA275THR, ASN34ILE, SER95ILE, ARG93TRP, ARG91TRP, a 3-bp [[Insertion (genetics)|insertion]] (TYR292) and a 12-bp [[Deletion (genetics)|deletion]] (1022_1033del) in exon 6, have been shown to cause GLUT1 deficiency syndrome 2 (GLUT1DS2), a clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced [[dyskinesia]]. The dyskinesia involves transient abnormal involuntary [[Movement disorders|movements]], such as [[dystonia]] and [[choreoathetosis]], induced by exercise or exertion, and affecting the exercised limbs. Some patients may also have [[epilepsy]], most commonly [[childhood absence epilepsy]]. Mild mental retardation may also occur. In some patients involuntary exertion-induced dystonic, choreoathetotic, and [[ballistic movement]]s may be associated with [[Macrocytic anemia|macrocytic]] [[hemolytic anemia]].<ref name=":0" /><ref name=":3" /> Inheritance of this disease is autosomal dominant.<ref name=":1" />

=== Idiopathic generalized epilepsy 12 ===
Some mutations, particularly ASN411SER, ARG458TRP, ARG223PRO and ARG232CYS, have been shown to cause idiopathic generalized epilepsy 12 (EIG12), a disorder characterized by recurring generalized seizures in the absence of detectable [[brain]] [[lesion]]s and/or [[Metabolic disorder|metabolic abnormalities]]. Generalized seizures arise diffusely and simultaneously from both [[Cerebral hemisphere|hemispheres of the brain]]. Seizure types include [[Juvenile myoclonic epilepsy|juvenile myoclonic seizures]], [[absence seizure]]s, and [[Generalized tonic–clonic seizure|generalized tonic-clonic seizures]]. In some EIG12 patients seizures may remit with age.<ref name=":0" /><ref name=":3" /> Inheritance of this disease is autosomal dominant.<ref name=":1" />

=== Dystonia 9 ===
Another mutation, ARG212CYS, has been shown to cause Dystonia 9 (DYT9), an autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic [[paraplegia]]. Most patients show some degree of cognitive impairment. Other variable features may include seizures, [[migraine]] headaches, and ataxia.<ref name=":0" /><ref name=":3" />

=== Stomatin-deficient cryohydrocytosis ===
Certain mutations, like GLY286ASP and a 3-bp deletion in ILE435/436, cause [[stomatin]]-deficient cryohydrocytosis with neurologic defects, a rare form of stomatocytosis characterized by episodic [[hemolytic anemia]], cold-induced red cells [[Ion#Anions and cations|cation]] leak, erratic [[hyperkalemia]], [[Neonatal jaundice|neonatal hyperbilirubinemia]], [[hepatosplenomegaly]], [[cataract]]s, seizures, mental retardation, and movement disorder.<ref name=":0" /><ref name=":3" /> Inheritance of this disease is autosomal dominant.<ref name=":1" />

=== Role as a receptor for HTLV ===
GLUT1 is also a receptor used by the [[Human T-lymphotropic virus|HTLV]] virus to gain entry into target cells.<ref>{{cite journal | vauthors = Manel N, Kim FJ, Kinet S, Taylor N, Sitbon M, Battini JL | title = The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV | journal = Cell | volume = 115 | issue = 4 | pages = 449–59 | date = November 2003 | pmid = 14622599 | doi = 10.1016/S0092-8674(03)00881-X | s2cid = 14399680 | doi-access = free }}</ref>

=== Role as a histochemical marker for hemangioma ===
Glut1 has also been demonstrated as a powerful histochemical marker for [[hemangioma]] of infancy<ref name="pmid10665907">{{cite journal | vauthors = North PE, Waner M, Mizeracki A, Mihm MC | title = GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas | journal = Human Pathology | volume = 31 | issue = 1 | pages = 11–22 | date = January 2000 | pmid = 10665907 | doi = 10.1016/S0046-8177(00)80192-6 | url = http://www.humanpathol.com/article/S0046-8177(00)80192-6/abstract | url-access = subscription }}</ref>

== Interactions ==

GLUT1 has been shown to [[Protein-protein interaction|interact]] with [[GIPC1]].<ref name="pmid10198040">{{cite journal | vauthors = Bunn RC, Jensen MA, Reed BC | title = Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a link between GLUT1 and the cytoskeleton | journal = Molecular Biology of the Cell | volume = 10 | issue = 4 | pages = 819–32 | date = April 1999 | pmid = 10198040 | pmc = 25204 | doi = 10.1091/mbc.10.4.819 }}</ref> It is found in a [[protein complex|complex]] with adducin ([[ADD2]]) and Dematin ([[EPB49]]) and interacts (via C-terminus cytoplasmic region) with Dematin [[Protein isoform|isoform]] 2.<ref>{{cite journal | vauthors = Khan AA, Hanada T, Mohseni M, Jeong JJ, Zeng L, Gaetani M, Li D, Reed BC, Speicher DW, Chishti AH | title = Dematin and adducin provide a novel link between the spectrin cytoskeleton and human erythrocyte membrane by directly interacting with glucose transporter-1 | journal = The Journal of Biological Chemistry | volume = 283 | issue = 21 | pages = 14600–9 | date = May 2008 | pmid = 18347014 | pmc = 2386908 | doi = 10.1074/jbc.M707818200 | doi-access = free | bibcode = 2008JBiCh.28314600K }}</ref> It also interacts with [[SNX27]]; the interaction is required when [[endocytosis|endocytosed]] to prevent degradation in [[lysosome]]s and promote recycling to the plasma membrane.<ref>{{cite journal | vauthors = Steinberg F, Gallon M, Winfield M, Thomas EC, Bell AJ, Heesom KJ, Tavaré JM, Cullen PJ | title = A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport | journal = Nature Cell Biology | volume = 15 | issue = 5 | pages = 461–71 | date = May 2013 | pmid = 23563491 | pmc = 4052425 | doi = 10.1038/ncb2721 }}</ref> This protein interacts with [[STOM]].<ref>{{cite journal | vauthors = Rungaldier S, Oberwagner W, Salzer U, Csaszar E, Prohaska R | title = Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1828 | issue = 3 | pages = 956–66 | date = March 2013 | pmid = 23219802 | pmc = 3790964 | doi = 10.1016/j.bbamem.2012.11.030 }}</ref> It interacts with [[SGTA]] (via Gln-rich region) and has binary interactions with [[CREB|CREB3-2]].<ref name=":0" /><ref name=":3" />

GLUT1 has two significant types in the brain: 45-kDa and 55-kDa. GLUT1 45-kDa is present in astroglia and neurons. GLUT1 55-kDa is present in the endothelial cells of the brain vasculature and is responsible for glucose transport across the blood–brain barrier; its deficiency causes a low level of glucose in CSF (less than 60&nbsp;mg/dl) which may elicit seizures in deficient individuals.{{citation needed|date=November 2015}}

Recently a GLUT1 inhibitor DERL3 has been described and is often methylated in colorectal cancer. In this cancer, DERL3 methylations seem to mediate the Warburg effect.<ref>{{cite journal | vauthors = Lopez-Serra P, Marcilla M, Villanueva A, Ramos-Fernandez A, Palau A, Leal L, Wahi JE, Setien-Baranda F, Szczesna K, Moutinho C, Martinez-Cardus A, Heyn H, Sandoval J, Puertas S, Vidal A, Sanjuan X, Martinez-Balibrea E, Viñals F, Perales JC, Bramsem JB, Ørntoft TF, Andersen CL, Tabernero J, McDermott U, Boxer MB, Vander Heiden MG, Albar JP, Esteller M | title = A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect | journal = Nature Communications | volume = 5 | pages = 3608 | date = April 2014 | issue = 1 | pmid = 24699711 | pmc = 3988805 | doi = 10.1038/ncomms4608 | bibcode = 2014NatCo...5.3608L }}</ref>

==Inhibitors==
Fasentin is a small molecule inhibitor of the intracellular domain of GLUT1 preventing glucose uptake.<ref name="pmid19001437">{{cite journal | vauthors = Wood TE, Dalili S, Simpson CD, Hurren R, Mao X, Saiz FS, Gronda M, Eberhard Y, Minden MD, Bilan PJ, Klip A, Batey RA, Schimmer AD | title = A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death | journal = Molecular Cancer Therapeutics | volume = 7 | issue = 11 | pages = 3546–55 | date = November 2008 | pmid = 19001437 | doi = 10.1158/1535-7163.MCT-08-0569 | s2cid = 7706108 | doi-access = free }}</ref>

Recently, a new more selective GLUT1 inhibitor, Bay-876, has been described.<ref name="pmid27552707">{{cite journal |vauthors=Siebeneicher H, Cleve A, Rehwinkel H, Neuhaus R, Heisler I, Müller T, Bauser M, Buchmann B |title=Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY-876 |journal=ChemMedChem |volume=7 |issue=11 |pages=3546–55 |date=October 2016 |pmid=27552707 |pmc=5095872 |doi=10.1002/cmdc.201600276 |doi-access=free}}</ref>

Recent experiments have shown that inhibition of glucose metabolism, particularly glycolysis, impairs mesodermal migration. This finding suggests that glycolysis is crucial for mesodermal cell motility and proper developmental progression. Inhibitors such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (BrPA), which block glycolytic enzymes, reduce the distance over which mesodermal cells migrate, supporting the hypothesis that glycolysis regulates mesodermal movement during early development.<ref name=dc/>

In functional assays, mesoderm explants treated with inhibitors of glycolysis or ERK signaling exhibited reduced migration without a corresponding increase in proliferation, further demonstrating that glycolysis drives mesodermal migration, not just cell division. These findings suggest that glycolytic activity, rather than cell proliferation, is the primary driver of mesoderm expansion during gastrulation.<ref name=dc/>

==Interactive pathway map==
{{GlycolysisGluconeogenesis_WP534|highlight=GLUT1}}

== References ==
{{reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Cao D, Bergmann J, Zhong L, Hemalatha A, Dingare C, Jensen T, Cox AL, Greco V, Steventon B, Sozen B | title = Selective utilization of glucose metabolism guides mammalian gastrulation | journal = Nature | volume = 634 | issue = 8035 | pages = 919–928 | date = October 2024 | pmid = 39415005 | pmc = 11499262 | doi = 10.1038/s41586-024-08044-1 | bibcode = 2024Natur.634..919C }}
* {{cite journal | vauthors = Lankford J, Butler IJ, Koenig MK | title = Glucose transporter type I deficiency causing mitochondrial dysfunction | journal = Journal of Child Neurology | volume = 27 | issue = 6 | pages = 796–8 | date = June 2012 | pmid = 22156785 | doi = 10.1177/0883073811426503 | s2cid = 206549634 }}
* {{cite journal | vauthors = North PE, Waner M, Mizeracki A, Mihm MC | title = GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas | journal = Human Pathology | volume = 31 | issue = 1 | pages = 11–22 | date = January 2000 | pmid = 10665907 | doi = 10.1016/S0046-8177(00)80192-6 }}
* {{cite journal | vauthors = Hruz PW, Mueckler MM | title = Structural analysis of the GLUT1 facilitative glucose transporter (review) | journal = Molecular Membrane Biology | volume = 18 | issue = 3 | pages = 183–93 | year = 2001 | pmid = 11681785 | doi = 10.1080/09687680110072140 | s2cid = 218897534 | doi-access = free }}
* {{cite journal | vauthors = Baumann MU, Deborde S, Illsley NP | title = Placental glucose transfer and fetal growth | journal = Endocrine | volume = 19 | issue = 1 | pages = 13–22 | date = October 2002 | pmid = 12583599 | doi = 10.1385/ENDO:19:1:13 | s2cid = 26301249 }}
* {{cite journal | vauthors = Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA | title = Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes | journal = Histology and Histopathology | volume = 20 | issue = 4 | pages = 1327–38 | date = October 2005 | pmid = 16136514 | doi = 10.14670/HH-20.1327 }}
{{refend}}

== External links ==
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=glut1  GeneReviews/NIH/UW entry on Glucose Transporter Type 1 Deficiency Syndrome]
* {{MeshName|Glucose+Transporter+Type+1}}
* {{PDBe-KB2|P11166|Solute carrier family 2, facilitated glucose transporter member 1}}

{{Solute carrier family|bg|bg0}}
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[[Category:Integral membrane proteins]]
[[Category:Solute carrier family]]