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Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a
transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
carrier
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that enables protein facilitated
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
movement across
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s. It is the principal transporter for transfer of glucose between
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
and
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
Unlike
GLUT4 Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the ''SLC2A4'' gene. GLUT4 is the insulin-regulated glucose transporter found primarily in a ...
, it does not rely on insulin for facilitated diffusion. In humans, this protein is encoded by the ''SLC2A2''
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.


Tissue distribution

GLUT2 is found in cellular membranes of: *
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
(Primary) *
pancreatic β cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimin ...
(Primary in mice, tertiary in humans after
GLUT1 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. GLUT1 facilitates the transport of glucose across ...
and GLUT3) *
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
(Not overly significant) * basolateral membrane of small intestine and apical GLUT2 is also suggested. * basolateral membrane of renal tubular cells


Function

GLUT2 has high capacity for glucose but low affinity (high ''K''M, ca. 15–20 mM) and thus functions as part of the "glucose sensor" in the pancreatic β-cells of rodents, though in human β-cells the role of GLUT2 seems to be a minor one. It is a very efficient carrier for
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. GLUT2 also carries
glucosamine Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most ...
. When the glucose concentration in the lumen of the small intestine goes above 30 mM, such as occurs in the fed-state, GLUT2 is up-regulated at the
brush border A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and their ...
membrane, enhancing the capacity of glucose transport. Basolateral GLUT2 in enterocytes also aids in the transport of fructose into the bloodstream through glucose-dependent
cotransport In Cellular Biology, cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane Second law of thermodynamics, from a region of lower concentration to a region of higher concentration—against the concentra ...
.


Clinical significance

Defects in the ''SLC2A2'' gene are associated with a particular type of glycogen storage disease called Fanconi-Bickel syndrome. In drug-treated diabetic pregnancies in which glucose levels in the woman are uncontrolled, neural tube and cardiac defects in the early-developing brain, spine, and heart depend upon functional GLUT2 carriers, and defects in the GLUT2 gene have been shown to be protective against such defects in rats. However, whilst a lack of GLUT2 adaptability is negative, it is important to remember the fact that the main result of untreated
gestational diabetes Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
appears to cause babies to be of above-average size, which may well be an advantage that is managed very well with a healthy GLUT2 status. Maintaining a regulated osmotic balance of sugar concentration between the blood circulation and the interstitial spaces is critical in some cases of edema including
cerebral edema Cerebral edema is excess accumulation of fluid ( edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compres ...
. GLUT2 appears to be particularly important to
osmoregulation Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...
, and preventing edema-induced stroke,
transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same symptoms associated with strokes, such as weakness or numbness on one side of ...
or coma, especially when blood glucose concentration is above average. GLUT2 could reasonably be referred to as the "
diabetic Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
glucose transporter" or a " stress hyperglycemia glucose transporter." SLC2A2 was associated with clinical stages and independently associated with overall survival in patients with HCC, and could be considered a new prognostic factor for HCC.


Interactive pathway map


See also

*
Glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporter ...


References


External links

* {{Solute carrier family, bg, bg0 Solute carrier family