GLUT2 explained

Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood^[1] Unlike GLUT4, it does not rely on insulin for facilitated diffusion.

In humans, this protein is encoded by the SLC2A2 gene.^{[2] [3]}

Tissue distribution

GLUT2 is found in cellular membranes of:

• liver (Primary)
• pancreatic β cell (Primary in mice, tertiary in humans after GLUT1 and GLUT3)^[4]
• hypothalamus (Not overly significant)
• basolateral membrane of small intestine and apical GLUT2 is also suggested.^[5]
• basolateral membrane of renal tubular cells^{[6] [7]}

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.^[8] It is a very efficient carrier for glucose.^{[9] [10]} Similarly, a recent study showed that lack of GLUT2 in β-cells doesn't impair glucose homeostasis or glucose-stimulated insulin secretion in mice.^[11]

GLUT2 also carries glucosamine.^[12]

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 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.Recent studies show that renal GLUT2 contributes to systemic glucose homeostasis by regulating glucose reabsorption. Lack of renal Glut2 reversed features of diabetes and obesity in mice. In addition, renal Glut2 deficiency caused knockdown of renal Sglt2 through the transcription factor Hnf1α.

Clinical significance

Defects in the SLC2A2 gene are associated with a particular type of glycogen storage disease called Fanconi-Bickel syndrome.^[13]

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.^[14] However, whilst a lack of GLUT2 adaptability^[15] is negative, it is important to remember the fact that the main result of untreated gestational diabetes 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.

GLUT2 appears to be particularly important to osmoregulation, and preventing edema-induced stroke, transient ischemic attack or coma, especially when blood glucose concentration is above average.^[16] GLUT2 could reasonably be referred to as the "diabetic glucose transporter" or a "stress hyperglycemia glucose transporter."

SLC2A2 was associated with clinical stages and independently associated with overall survival in patients with Hepatocellular carcinoma, and could be considered a new prognostic factor for HCC.^[17]

See also

• Glucose transporter

Notes and References

1. Gwyn W. Gould . Helen M. Thomas . Thomas J. Jess . Graeme I. Bell . Expression of human glucose transporters in Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte, liver, and brain isoforms . Biochemistry . 30 . 21 . 5139–5145 . May 1991. 10.1021/bi00235a004 . 2036379.
2. Froguel P, Zouali H, Sun F, Velho G, Fukumoto H, Passa P, Cohen D . CA repeat polymorphism in the glucose transporter GLUT 2 gene . Nucleic Acids Research . 19 . 13 . 3754 . July 1991 . 1852621 . 328421 . 10.1093/nar/19.13.3754-a .
3. Uldry M, Thorens B . The SLC2 family of facilitated hexose and polyol transporters . Pflügers Archiv . 447 . 5 . 480–9 . February 2004 . 12750891 . 10.1007/s00424-003-1085-0 . 25539725 .
4. McCulloch LJ, van de Bunt M, Braun M, Frayn KN, CLark A, Gloyn AL . GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus . Molecular Genetics and Metabolism . 104 . 4 . 648–53 . December 2011 . 21920790 . 10.1016/j.ymgme.2011.08.026.
5. Kellett GL, Brot-Laroche E . Apical GLUT2: a major pathway of intestinal sugar absorption . Diabetes . 54 . 10 . 3056–62 . October 2005 . 16186415 . 10.2337/diabetes.54.10.3056 . free .
6. Freitas HS, Schaan BD, Seraphim PM, Nunes MT, Machado UF . Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats . Molecular and Cellular Endocrinology . 237 . 1–2 . 49–57 . June 2005 . 15869838 . 10.1016/j.mce.2005.03.005 . 44856595 .
7. de Souza Cordeiro . Leticia Maria . Bainbridge . Lauren . Devisetty . Nagavardhini . McDougal . David H. . Peters . Dorien J. M. . Chhabra . Kavaljit H. . 2022 . Loss of function of renal Glut2 reverses hyperglycaemia and normalises body weight in mouse models of diabetes and obesity . Diabetologia . 65 . 6 . 1032–1047 . 10.1007/s00125-022-05676-8 . 9081162 . 35290476.
8. McCulloch LJ, van de Bunt M, Braun M, Frayn KN, Clark A, Gloyn AL . GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus . Molecular Genetics and Metabolism . 104 . 4 . 648–53 . December 2011 . 21920790 . 10.1016/j.ymgme.2011.08.026 .
9. Guillam MT, Hümmler E, Schaerer E, Yeh JI, Birnbaum MJ, Beermann F, Schmidt A, Dériaz N, Thorens B, Wu JY . Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2 . Nature Genetics . 17 . 3 . 327–30 . November 1997 . 9354799 . 10.1038/ng1197-327 . 37328600 .
10. Efrat S . Making sense of glucose sensing . Nature Genetics . 17 . 3 . 249–50 . November 1997 . 9354775 . 10.1038/ng1197-249 . 13219161 .
11. Bathina . Siresha . Faniyan . Tumininu S. . Bainbridge . Lauren . Davis . Autumn . Chhabra . Kavaljit H. . 2023 . Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice . Biomolecules . 13 . 3 . 540 . 10.3390/biom13030540 . 36979475. free . 10046365 .
12. Uldry M, Ibberson M, Hosokawa M, Thorens B . GLUT2 is a high affinity glucosamine transporter . FEBS Letters . 524 . 1–3 . 199–203 . July 2002 . 12135767 . 10.1016/S0014-5793(02)03058-2 . 40913482 . free .
13. Santer R, Groth S, Kinner M, Dombrowski A, Berry GT, Brodehl J, Leonard JV, Moses S, Norgren S, Skovby F, Schneppenheim R, Steinmann B, Schaub J . The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome . Human Genetics . 110 . 1 . 21–9 . January 2002 . 11810292 . 10.1007/s00439-001-0638-6 . 1767168 .
14. Li R, Thorens B, Loeken MR . Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy . Diabetologia . 50 . 3 . 682–9 . March 2007 . 17235524 . 10.1007/s00125-006-0579-7 . free .
15. Thomson AB, Wild G . Adaptation of intestinal nutrient transport in health and disease. Part I . Digestive Diseases and Sciences . 42 . 3 . 453–69 . March 1997 . 9073126 . 10.1023/A:1018807120691 . 25371741 .
16. Stolarczyk E, Le Gall M, Even P, Houllier A, Serradas P, Brot-Laroche E, Leturque A . Loss of sugar detection by GLUT2 affects glucose homeostasis in mice . PLOS ONE . 2 . 12 . e1288 . December 2007 . 18074013 . 2100167 . 10.1371/journal.pone.0001288 . 2007PLoSO...2.1288S . Maedler . Kathrin . free .
17. Kim. Yun Hak. Jeong. Dae Cheon. Pak. Kyoungjune. Han. Myoung-Eun. Kim. Ji-Young. Liangwen. Liu. Kim. Hyun Jin. Kim. Tae Woo. Kim. Tae Hwa. Hyun. Dong Woo. Oh. Sae-Ock. 2017-09-15. SLC2A2 (GLUT2) as a novel prognostic factor for hepatocellular carcinoma. Oncotarget. en. 8. 40. 68381–68392. 10.18632/oncotarget.20266. 28978124. 5620264. 1949-2553.