Sodium/glucose cotransporter 2

The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 (solute carrier family 5 (sodium/glucose cotransporter)) gene.[5]

SLC5A2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSLC5A2, SGLT2, solute carrier family 5 member 2
External IDsOMIM: 182381 MGI: 2181411 HomoloGene: 2289 GeneCards: SLC5A2
Orthologs
SpeciesHumanMouse
Entrez

6524

246787

Ensembl

ENSG00000140675

ENSMUSG00000030781

UniProt

P31639

Q923I7

RefSeq (mRNA)

NM_003041

NM_133254

RefSeq (protein)

NP_003032

NP_573517

Location (UCSC)Chr 16: 31.48 – 31.49 MbChr 7: 127.86 – 127.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

SGLT2 is a member of the sodium glucose cotransporter family, which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney.[6] SGLT2 is located in the early proximal tubule, and is responsible for reabsorption of 80-90% of the glucose filtered by the kidney glomerulus.[7] Most of the remaining glucose absorption is by sodium/glucose cotransporter 1 (SGLT1) in more distal sections of the proximal tubule.[8]

SGLT2 inhibitors for diabetes

SGLT2 inhibitors are called gliflozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of type II diabetes. Gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure.[9] The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to euglycemic ketoacidosis.[10][11] Other side effects of gliflozins include increased risk of Fournier gangrene[12] and of (generally mild) genital infections such as candidal vulvovaginitis.[13]

Clinical significance

Mutations in this gene are also associated with renal glycosuria.[14]

Model organisms

Model organisms have been used in the study of SLC5A2 function. A conditional knockout mouse line, called Slc5a2tm1a(KOMP)Wtsi[20][21] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[22][23][24] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[18][25] Twenty-two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males displayed increased drinking behaviour.[18]

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000140675 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030781 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wells RG, Mohandas TK, Hediger MA (Sep 1993). "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics. 17 (3): 787–9. doi:10.1006/geno.1993.1411. PMID 8244402.
  6. "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".
  7. Bonora BM, Avogaro A, Fadini GP (2020). "Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13: 161–174. doi:10.2147/DMSO.S233538. PMC 6982447. PMID 32021362.
  8. Vallon V, Thomson SC (2012). "Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney". Annual Review of Physiology. 74: 351–375. doi:10.1146/annurev-physiol-020911-153333. PMC 3807782. PMID 22335797.
  9. Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD (2014). "Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin". Nutrition & Diabetes. 4 (11): e143. doi:10.1038/nutd.2014.40. PMC 4259905. PMID 25365416.
  10. Rawla, P; Vellipuram, AR; Bandaru, SS; Pradeep Raj, J (2017). "Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma". Endocrinology, Diabetes & Metabolism Case Reports. 2017. doi:10.1530/EDM-17-0081. PMC 5592704. PMID 28924481.
  11. "FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood". Food and Drug Administration, USA. 2015-05-15.
  12. "SGLT2 Inhibitors Associated with Fournier Gangrene". Jwatch.org. Retrieved 2019-05-06.
  13. "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
  14. Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (Mar 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney International. 69 (5): 852–5. doi:10.1038/sj.ki.5000194. PMID 16518345.
  15. "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute.
  16. "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute.
  17. "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute.
  18. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  19. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  20. "International Knockout Mouse Consortium".
  21. "Mouse Genome Informatics".
  22. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  23. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  24. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  25. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.