SGLT2

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Solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
Symbols SLC5A2 ; SGLT2
External IDs OMIM182381 MGI2181411 HomoloGene2289 IUPHAR: 916 ChEMBL: 3884 GeneCards: SLC5A2 Gene
Orthologs
Species Human Mouse
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:
31.49 – 31.5 Mb
Chr 7:
128.27 – 128.27 Mb
PubMed search [1] [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.[1]

Function[edit]

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.[2]

SGLT2 inhibitors for diabetes[edit]

Main article: Gliflozin

SGLT2 inhibitors are called gliflozins and lead to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type II diabetes. As studied on canagliflozin, a member of this class of drugs, gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure.[3] The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis.[4] Other side effects of gliflozins include increased risk of (generally mild) urinary tract infections, candidal vulvovaginitis and hypoglycemia.[5]

Clinical significance[edit]

Mutations in this gene are also associated with renal glucosuria.[6]

Model organisms[edit]

Model organisms have been used in the study of SLC5A2 function. A conditional knockout mouse line, called Slc5a2tm1a(KOMP)Wtsi[12][13] 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.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males displayed increased drinking behaviour.[10]

See also[edit]

References[edit]

  1. ^ 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): 787–9. doi:10.1006/geno.1993.1411. PMID 8244402. 
  2. ^ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)". 
  3. ^ Haas, B; Eckstein, N; Pfeifer, V; Mayer, P; Hass, M D S (2014). "Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin". Nutrition & Diabetes 4 (11): e143. doi:10.1038/nutd.2014.40. ISSN 2044-4052. 
  4. ^ "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. 
  5. ^ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19. 
  6. ^ Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (March 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney Int. 69 (5): 852–5. doi:10.1038/sj.ki.5000194. PMID 16518345. 
  7. ^ "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute. 
  8. ^ "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute. 
  9. ^ "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute. 
  10. ^ a b c 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. 
  11. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  12. ^ "International Knockout Mouse Consortium". 
  13. ^ "Mouse Genome Informatics". 
  14. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  15. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  16. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  17. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading[edit]