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.[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 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
| 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 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
References
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".
- ^ 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.
- ^ "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.
- ^ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute.
- ^ "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute.
- ^ 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.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium".
- ^ "Mouse Genome Informatics".
- ^ 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.
- ^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
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)