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{{Short description|Protein}}
{{Infobox gene}}

'''Glucose transporter 3''' (or '''GLUT3'''), also known as '''solute carrier family 2, facilitated glucose transporter member 3''' (SLC2A3) is a [[protein]] that in humans is encoded by the ''SLC2A3'' [[gene]].<ref name="pmid3170580">{{cite journal |vauthors=Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI | title = Evidence for a family of human glucose transporter-like proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. | journal = J Biol Chem | volume = 263 | issue = 30 | pages = 15245–8 |date=October 1988 | doi = 10.1016/S0021-9258(19)37577-5 | pmid = 3170580 | doi-access = free }}</ref> GLUT3 [[facilitated diffusion|facilitates]] the transport of [[glucose]] across the [[cell membrane|plasma membranes]] of mammalian cells. GLUT3 is most known for its specific expression in [[neuron]]s and has originally been designated as the neuronal [[glucose transporter|GLUT]]. GLUT3 has been studied in other cell types with specific glucose requirements, including [[sperm]], preimplantation [[embryo]]s, circulating [[white blood cell]]s and [[carcinoma]] [[cell line]]s.<ref name="pmid18577699">{{cite journal |vauthors=Simpson IA, Dwyer D, Malide D, Moley KH, Travis A, Vannucci SJ |title=The facilitative glucose transporter GLUT3: 20 years of distinction |journal=Am. J. Physiol. Endocrinol. Metab. |volume=295 |issue=2 |pages=E242–53 |date=August 2008 |pmid=18577699 |pmc=2519757 |doi=10.1152/ajpendo.90388.2008 }}</ref>

==Discovery==

GLUT3 was the third [[glucose transporter]] to be discovered, first cloned in 1988 from a fetal skeletal muscle cell line, using a [[GLUT1]] cDNA probe and shown to share 64.4% identity with GLUT1.<ref name="pmid3170580"/>

==Function==

Although GLUT3 was found to be expressed in various tissues, it is most specifically expressed in neurons, found predominantly in axons and dendrites and also, but less prominently, in the cell body.<ref name="pmid9298843">{{cite journal |vauthors=Vannucci SJ, Maher F, Simpson IA |title=Glucose transporter proteins in brain: delivery of glucose to neurons and glia |journal=Glia |volume=21 |issue=1 |pages=2–21 |date=September 1997 |pmid=9298843 |doi= 10.1002/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C|s2cid=13501112 }}</ref> GLUT3 has at least a fivefold greater transport capacity than GLUT1 or GLUT4, as well as a higher glucose affinity than GLUT1, GLUT2 or GLUT4.  This is significant as glucose levels surrounding the neurons are only 1–2 mM, compared to 5–6 mM in the serum.<ref name="pmid18577699"/>

===Brain===

Glucose delivery and use in the mammalian brain is mediated primarily by a high molecular weight form of GLUT1 in the blood–brain barrier, GLUT3 in neuronal populations and a less glycosylated form of GLUT1 in the remainder of the parenchyma. GLUT3 is considered the main but not the exclusive neuronal glucose transporter, whereas other glucose transporters have also been observed in neurons.<ref name="pmid9298843"/>

GLUT3 expression in neurons in the rat coincides with maturation and synaptic connectivity<ref name="pmid9778574">{{cite journal |vauthors=Vannucci SJ, Clark RR, Koehler-Stec E |title=Glucose transporter expression in brain: relationship to cerebral glucose utilization |journal=Dev. Neurosci. |volume=20 |issue=4–5 |pages=369–79 |year=1998 |pmid=9778574 |doi= 10.1159/000017333|s2cid=46874239 |url=https://zenodo.org/record/1235307|display-authors=etal}}</ref> and a positive correlation between protein levels of GLUT1, GLUT3 and regional cerebral glucose use was observed in mouse.<ref name="pmid10070152">{{cite journal |vauthors=Khan JY, Rajakumar RA, McKnight RA, Devaskar UP, Devaskar SU |title=Developmental regulation of genes mediating murine brain glucose uptake |journal=Am. J. Physiol. |volume=276 |issue=3 Pt 2 |pages=R892–900 |date=March 1999 |pmid=10070152 |doi= 10.1152/ajpregu.1999.276.3.R892|s2cid=11700280 }}</ref>

The central role of GLUT3 in cerebral metabolism has been challenged by the astrocyte-neuron lactate shuttle (ANLS) hypothesis,<ref name="pmid14600434">{{cite journal |vauthors=Pellerin L, Magistretti PJ |title=Food for thought: challenging the dogmas |journal=J. Cereb. Blood Flow Metab. |volume=23 |issue=11 |pages=1282–6 |date=November 2003 |pmid=14600434 |doi=10.1097/01.WCB.0000096064.12129.3D |doi-access=free }}</ref> which proposes that [[astrocyte]]s play the key role in the coupling of neuronal activity and cerebral glucose use. In this hypothesis, the astrocyte, which relies on GLUT1 for glucose transport, is the primary consumer of glucose in the brain, providing lactate as the primary energetic fuel for neurons. However, by modeling the kinetic characteristics and glucose concentrations in neurons and glia, it was concluded that the glucose capacity of neurons via GLUT3 far exceeds that of astrocytes via GLUT1.<ref name="pmid17579656">{{cite journal |vauthors=Simpson IA, Carruthers A, Vannucci SJ |title=Supply and demand in cerebral energy metabolism: the role of nutrient transporters |journal=J. Cereb. Blood Flow Metab. |volume=27 |issue=11 |pages=1766–91 |date=November 2007 |pmid=17579656 |pmc=2094104 |doi=10.1038/sj.jcbfm.9600521 }}</ref> Additionally, demonstrations of increase in GLUT3 expression associated with increased cerebral glucose use provides further confirmation of the central role of GLUT3.<ref name="pmid10070152"/>

===Other tissues===

Expression of GLUT3 is also found in sperm, embryos, white blood cells and carcinoma cell lines.

==Interactive pathway map==
{{GlycolysisGluconeogenesis_WP534|highlight=GLUT3}}

==References==
{{reflist}}

==External links==
* {{MeshName|Glucose+Transporter+Type+3}}

{{Solute carrier family|bg|bg0}}
{{Nerve tissue protein}}

{{DEFAULTSORT:Glut3}}
[[Category:Solute carrier family]]