Sodium/glucose cotransporter 2

Template:PBB 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.

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.

SGLT2 inhibitors for diabetes

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. The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis. Other side effects of gliflozins include increased risk of (generally mild) urinary tract infections, candidal vulvovaginitis and hypoglycemia.

Clinical significance

Mutations in this gene are also associated with renal glucosuria.

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
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
Citrobacter infection	Normal
All tests and analysis from

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

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

See also

• SGLT Family
• Discovery and development of gliflozins

Further reading

• van den Heuvel LP, Assink K, Willemsen M, Monnens L (2002). "Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2)". Hum. Genet. 111 (6): 544–7. doi:10.1007/s00439-002-0820-5. PMID 12436245.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Santer R, Kinner M, Lassen CL; et al. (2003). "Molecular analysis of the SGLT2 gene in patients with renal glucosuria". J. Am. Soc. Nephrol. 14 (11): 2873–82. doi:10.1097/01.asn.0000092790.89332.d2. PMID 14569097. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Wells RG, Pajor AM, Kanai Y; et al. (1992). "Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter". Am. J. Physiol. 263 (3 Pt 2): F459-65. PMID 1415574. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Calado J, Sznajer Y, Metzger D; et al. (2008). "Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion". Nephrol. Dial. Transplant. 23 (12): 3874–9. doi:10.1093/ndt/gfn386. PMID 18622023. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Calado J, Soto K, Clemente C; et al. (2004). "Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria". Hum. Genet. 114 (3): 314–6. doi:10.1007/s00439-003-1054-x. PMID 14614622. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Magen D, Sprecher E, Zelikovic I, Skorecki K (2005). "A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria". Kidney Int. 67 (1): 34–41. doi:10.1111/j.1523-1755.2005.00053.x. PMID 15610225.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• 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". Int J Med Sci. 4 (3): 131–9. doi:10.7150/ijms.4.131. PMC 1868657. PMID 17505558.{{cite journal}}: CS1 maint: multiple names: authors list (link)