SGLT2

Solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
Symbols	SLC5A2 ; SGLT2
External IDs	OMIM: 182381 MGI: 2181411 HomoloGene: 2289 IUPHAR: 916 ChEMBL: 3884 GeneCards: SLC5A2 Gene
Gene ontology Molecular function • low-affinity glucose:sodium symporter activity Cellular component • plasma membrane • integral component of membrane • brush border membrane • extracellular exosome Biological process • carbohydrate metabolic process • transport • sodium ion transport • glucose transport • transmembrane transport Sources: Amigo / QuickGO
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: 31.48 – 31.49 Mb	Chr 7: 128.27 – 128.27 Mb
PubMed search

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

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

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 euglycemic ketoacidosis.^[4] Other side effects of gliflozins include increased risk of (generally mild) urinary tract infections, candidal vulvovaginitis and hypoglycemia.^[5]

Clinical significance

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

Model organisms

Slc5a2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Abnormal[7]
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal[8]
Citrobacter infection	Normal[9]
All tests and analysis from[10][11]

Model organisms have been used in the study of SLC5A2 function. A conditional knockout mouse line, called Slc5a2^{tm1a(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

• SGLT Family
• Discovery and development of gliflozins

References

1. 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.
2. "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".
3. 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. PMID 25365416.
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 (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.
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. 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 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.
15. Dolgin E (Jun 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 (Jan 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 Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• van den Heuvel LP, Assink K, Willemsen M, Monnens L (Dec 2002). "Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2)". Human Genetics 111 (6): 544–7. doi:10.1007/s00439-002-0820-5. PMID 12436245.
• Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D (Nov 2003). "Molecular analysis of the SGLT2 gene in patients with renal glucosuria". Journal of the American Society of Nephrology 14 (11): 2873–82. doi:10.1097/01.asn.0000092790.89332.d2. PMID 14569097.
• Wells RG, Pajor AM, Kanai Y, Turk E, Wright EM, Hediger MA (Sep 1992). "Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter". The American Journal of Physiology 263 (3 Pt 2): F459–65. PMID 1415574.
• Calado J, Sznajer Y, Metzger D, Rita A, Hogan MC, Kattamis A, Scharf M, Tasic V, Greil J, Brinkert F, Kemper MJ, Santer R (Dec 2008). "Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion". Nephrology, Dialysis, Transplantation 23 (12): 3874–9. doi:10.1093/ndt/gfn386. PMID 18622023.
• Calado J, Soto K, Clemente C, Correia P, Rueff J (Feb 2004). "Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria". Human Genetics 114 (3): 314–6. doi:10.1007/s00439-003-1054-x. PMID 14614622.
• Magen D, Sprecher E, Zelikovic I, Skorecki K (Jan 2005). "A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria". Kidney International 67 (1): 34–41. doi:10.1111/j.1523-1755.2005.00053.x. PMID 15610225.
• Castaneda F, Burse A, Boland W, Kinne RK (2007). "Thioglycosides as inhibitors of hSGLT1 and hSGLT2: potential therapeutic agents for the control of hyperglycemia in diabetes". International Journal of Medical Sciences 4 (3): 131–9. doi:10.7150/ijms.4.131. PMC 1868657. PMID 17505558.