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Sodium/glucose cotransporter 2

From Wikipedia, the free encyclopedia

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; OMA:SLC5A2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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]

Function

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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

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SGLT2 inhibitors are also called gliflozins or flozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of type 2 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

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

Sodium-glucose cotransporter-2 (SGLT2) inhibitors were associated with significant long-term reductions in mortality risk for patients with pulmonary arterial hypertension (PAH), according to an observational cohort study.[15] The study revealed that after one year, 8.1% of PAH patients prescribed SGLT2 inhibitors had died, compared to 15.5% of those who did not take the medication.

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140675Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030781Ensembl, 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 (September 1993). "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics. 17 (3): 787–789. 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. 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 (November 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, et al. (March 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney International. 69 (5): 852–855. doi:10.1038/sj.ki.5000194. PMID 16518345.
  15. ^ Lemonjava I, Gudushauri N, Tskhakaia I, Martinez Manzano JM, Azmaiparashvili Z (2024). "Impact of Sglt2 Inhibitors on Mortality in Pulmonary Arterial Hypertension: Exploring the Association". Chest. 166 (4): A5793. doi:10.1016/j.chest.2024.06.3435.

Further reading

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