Biology:SGLT2
 Generic protein structure example |
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. They lead to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type II diabetes. 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) genital infections, such as candidal vulvovaginitis.[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
- SGLT Family
- Discovery and development of gliflozins
References
- ↑ "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics 17 (3): 787–9. Sep 1993. doi:10.1006/geno.1993.1411. PMID 8244402.
- ↑ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6524.
- ↑ "Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin". Nutrition & Diabetes 4 (11): e143. 2014. doi:10.1038/nutd.2014.40. PMID 25365416.
- ↑ "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. http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm.
- ↑ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. http://www.diabetes.co.uk/diabetes-medication/sglt2-inhibitors.html. Retrieved 2015-05-19.
- ↑ "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney International 69 (5): 852–5. Mar 2006. doi:10.1038/sj.ki.5000194. PMID 16518345.
- ↑ "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/indirect-calorimetry/.
- ↑ "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/salmonella-challenge/.
- ↑ "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/citrobacter-challenge/.
- ↑ 10.0 10.1 10.2 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". http://www.knockoutmouse.org/martsearch/search?query=Slc5a2.
- ↑ "Mouse Genome Informatics". http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4363573.
- ↑ "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. Jun 2011. doi:10.1038/nature10163. PMID 21677750.
- ↑ "Mouse library set to be knockout". Nature 474 (7351): 262–3. Jun 2011. doi:10.1038/474262a. PMID 21677718.
- ↑ "A mouse for all reasons". Cell 128 (1): 9–13. Jan 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. 2011. doi:10.1186/gb-2011-12-6-224. PMID 21722353.
Further reading
- "Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2)". Human Genetics 111 (6): 544–7. Dec 2002. doi:10.1007/s00439-002-0820-5. PMID 12436245.
- "Molecular analysis of the SGLT2 gene in patients with renal glucosuria". Journal of the American Society of Nephrology 14 (11): 2873–82. Nov 2003. doi:10.1097/01.asn.0000092790.89332.d2. PMID 14569097.
- "Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter". The American Journal of Physiology 263 (3 Pt 2): F459-65. Sep 1992. PMID 1415574.
- "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. Dec 2008. doi:10.1093/ndt/gfn386. PMID 18622023.
- "Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria". Human Genetics 114 (3): 314–6. Feb 2004. doi:10.1007/s00439-003-1054-x. PMID 14614622.
- "A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria". Kidney International 67 (1): 34–41. Jan 2005. doi:10.1111/j.1523-1755.2005.00053.x. PMID 15610225.
- "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. 2007. doi:10.7150/ijms.4.131. PMID 17505558.
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