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Gene Review

SLC5A2  -  solute carrier family 5 (sodium/glucose...

Homo sapiens

Synonyms: Low affinity sodium-glucose cotransporter, Na(+)/glucose cotransporter 2, SGLT2, Sodium/glucose cotransporter 2, Solute carrier family 5 member 2
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Disease relevance of SLC5A2

  • Further investigations aimed at identifying the presence of a second cotransporter that could be expressed erroneously in the colon cancer cell line were unsuccessful: T3-treatment did not modify the sugar-specificity profile of AMG transport and did not induce the expression of SGLT2 as assessed by reverse transcription-PCR [1].
  • These results suggest that SGLT2 plays a role in glucose uptake in the metastatic lesions of lung cancer [2].

High impact information on SLC5A2

  • By comparing the initial rate of [14C]-alpha MeGlc uptake with the Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the Na+ to glucose coupling ratio of SGLT2 is 1:1 [3].
  • In contrast to SGLT1, SGLT2 does not transport D-galactose [3].
  • We conclude that SGLT2 has properties characteristic of the renal low affinity high capacity Na+/glucose cotransporter as previously reported for perfused tubule preparations and brush border membrane vesicles [3].
  • In a hyperglycemic environment, HEPTECs isolated from patients with type 2 diabetes expressed significantly more SGLT2 and the facilitative glucose transporter GLUT2 than cells from healthy individuals [4].
  • Our results show that HNF1alpha directly controls SGLT2 gene expression [5].

Biological context of SLC5A2


Anatomical context of SLC5A2

  • The chromosomal location of the gene SGLT2, which is presumed to encode a low-affinity Na+/glucose cotransporter, has been determined using a panel of rodent-human somatic cell hybrids [7].
  • The level of SGLT2 expression was, however, significantly higher in the metastatic lesions of both the liver and lymph node than in the primary lung cancers [2].
  • In contrast, the expression of SGLT2 in human tissues appears to be ubiquitous, with levels ranging from 6.7E + 4 molecules/microg total RNA (in skeletal muscle) to 3.2E + 6 molecules/microg total RNA (in kidney), levels 10-100-fold higher than the expression of SGLT1 in the same tissues [8].
  • RESULTS: Messenger RNA expression for glucose transporter 1 (GLUT1) and SGLT-2 were reduced in trophoblast cells incubated with 4500 mg/L glucose compared with those incubated with 1000 and 2000 mg/L glucose. mRNA expression of CuZn-SOD was also decreased in trophoblasts incubated with 4500 mg/L glucose [9].
  • This indicates that SGLT2 may play a role in milk synthesis in the lactating mammary gland [10].

Associations of SLC5A2 with chemical compounds

  • Autoradiography showed that methyl-D-glucoside was accumulated throughout the renal cortex, suggesting that both sodium-D-glucose cotransporters expressed in kidney, SGLT1 and SGLT2, are involved in the uptake [11].
  • Isolated renal glucosuria results from mutations in SGLT2, which codes for an active transporter specific for d-glucose and expressed in the luminal membrane of the renal proximal tubule [12].

Other interactions of SLC5A2


Analytical, diagnostic and therapeutic context of SLC5A2


  1. Thyroid hormone regulation of the Na+/glucose cotransporter SGLT1 in Caco-2 cells. Matosin-Matekalo, M., Mesonero, J.E., Delezay, O., Poiree, J.C., Ilundain, A.A., Brot-Laroche, E. Biochem. J. (1998) [Pubmed]
  2. SGLT gene expression in primary lung cancers and their metastatic lesions. Ishikawa, N., Oguri, T., Isobe, T., Fujitaka, K., Kohno, N. Jpn. J. Cancer Res. (2001) [Pubmed]
  3. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. Kanai, Y., Lee, W.S., You, G., Brown, D., Hediger, M.A. J. Clin. Invest. (1994) [Pubmed]
  4. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Rahmoune, H., Thompson, P.W., Ward, J.M., Smith, C.D., Hong, G., Brown, J. Diabetes (2005) [Pubmed]
  5. HNF1alpha controls renal glucose reabsorption in mouse and man. Pontoglio, M., Prié, D., Cheret, C., Doyen, A., Leroy, C., Froguel, P., Velho, G., Yaniv, M., Friedlander, G. EMBO Rep. (2000) [Pubmed]
  6. A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria. Magen, D., Sprecher, E., Zelikovic, I., Skorecki, K. Kidney Int. (2005) [Pubmed]
  7. Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere. Wells, R.G., Mohandas, T.K., Hediger, M.A. Genomics (1993) [Pubmed]
  8. Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1). Zhou, L., Cryan, E.V., D'Andrea, M.R., Belkowski, S., Conway, B.R., Demarest, K.T. J. Cell. Biochem. (2003) [Pubmed]
  9. High glucose levels down-regulate glucose transporter expression that correlates with increased oxidative stress in placental trophoblast cells in vitro. Li, H., Gu, Y., Zhang, Y., Lucas, M.J., Wang, Y. J. Soc. Gynecol. Investig. (2004) [Pubmed]
  10. Cloning and expression of bovine sodium/glucose cotransporter SGLT2. Zhao, F.Q., McFadden, T.B., Wall, E.H., Dong, B., Zheng, Y.C. J. Dairy Sci. (2005) [Pubmed]
  11. Synthesis and biologic evaluation of (11)c-methyl-d-glucoside, a tracer of the sodium-dependent glucose transporters. Bormans, G.M., Van Oosterwyck, G., De Groot, T.J., Veyhl, M., Mortelmans, L., Verbruggen, A.M., Koepsell, H. J. Nucl. Med. (2003) [Pubmed]
  12. Renal glucosuria due to SGLT2 mutations. Kleta, R., Stuart, C., Gill, F.A., Gahl, W.A. Mol. Genet. Metab. (2004) [Pubmed]
  13. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). van den Heuvel, L.P., Assink, K., Willemsen, M., Monnens, L. Hum. Genet. (2002) [Pubmed]
  14. Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Calado, J., Loeffler, J., Sakallioglu, O., Gok, F., Lhotta, K., Barata, J., Rueff, J. Kidney Int. (2006) [Pubmed]
  15. High glucose reduces albumin uptake in cultured proximal tubular cells (LLC-PK1). Ishibashi, F. Diabetes Res. Clin. Pract. (2004) [Pubmed]
  16. Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules. Velic, A., Hirsch, J.R., Bartel, J., Thomas, R., Schröter, R., Stegemann, H., Edemir, B., August, C., Schlatter, E., Gabriëls, G. J. Am. Soc. Nephrol. (2004) [Pubmed]
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