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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox gene}}
{{Infobox gene}}


The '''sodium/glucose cotransporter 2''' (SGLT2) is a [[protein]] that in humans is encoded by the {{gene|SLC5A2}} (solute carrier family 5 (sodium/glucose cotransporter)) [[gene]].<ref name="pmid8244402">{{cite journal | vauthors = Wells RG, Mohandas TK, Hediger MA | title = Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere | journal = Genomics | volume = 17 | issue = 3 | pages = 787–9 | date = Sep 1993 | pmid = 8244402 | doi = 10.1006/geno.1993.1411 }}</ref>
The '''sodium/glucose cotransporter 2''' (SGLT2) is a [[protein]] that in humans is encoded by the {{gene|SLC5A2}} (solute carrier family 5 (sodium/glucose cotransporter)) [[gene]].<ref name="pmid8244402">{{cite journal | vauthors = Wells RG, Mohandas TK, Hediger MA | title = Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere | journal = Genomics | volume = 17 | issue = 3 | pages = 787–9 | date = Sep 1993 | pmid = 8244402 | doi = 10.1006/geno.1993.1411 }}</ref>


== Function ==
== Function ==
SGLT2 is a member of the [[sodium-glucose transport proteins|sodium glucose cotransporter family]] which are sodium-dependent [[glucose]] transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney.<ref name="entrez">{{cite web | title = Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6524}}</ref> SGLT2 is located in the early [[proximal tubule]], and is responsible for [[reabsorption]] of 80-90% of the glucose filtered by the kidney [[Glomerulus (kidney)|glomerulus]].<ref name="pmid32021362">{{cite journal | vauthors=Bonora BM, Avogaro A, Fadini GP | title=Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence | journal=[[Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy]] | volume=13 | pages=161–174 | year=2020 | url= | doi = 10.2147/DMSO.S233538 | pmc=6982447 | pmid=32021362}}</ref> Most of the remaining glucose absorption is by [[sodium/glucose cotransporter 1]] (SGLT1) in more distal sections of the proximal tubule.<ref name="pmid22335797">{{cite journal | vauthors=Vallon V, Thomson SC | title=Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney | journal=[[Annual Review of Physiology]] | volume=74 | pages=351–375 | year=2012 | doi = 10.1146/annurev-physiol-020911-153333 | pmc=3807782 | pmid=22335797}}</ref>
SGLT2 is a member of the [[sodium-glucose transport proteins|sodium glucose cotransporter family]], which are sodium-dependent [[glucose]] transport proteins. SGLT2 is the major cotransporter involved in glucose [[reabsorption]] in the kidney.<ref name="entrez">{{cite web | title = Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6524}}</ref> SGLT2 is located in the early [[proximal tubule]], and is responsible for reabsorption of 80-90% of the glucose filtered by the kidney [[Glomerulus (kidney)|glomerulus]].<ref name="pmid32021362">{{cite journal | vauthors=Bonora BM, Avogaro A, Fadini GP | title=Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence | journal=[[Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy]] | volume=13 | pages=161–174 | year=2020 | url= | doi = 10.2147/DMSO.S233538 | pmc=6982447 | pmid=32021362 | doi-access=free }}</ref> Most of the remaining glucose absorption is by [[sodium/glucose cotransporter 1]] (SGLT1) in more distal sections of the proximal tubule.<ref name="pmid22335797">{{cite journal | vauthors=Vallon V, Thomson SC | title=Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney | journal=[[Annual Review of Physiology]] | volume=74 | pages=351–375 | year=2012 | doi = 10.1146/annurev-physiol-020911-153333 | pmc=3807782 | pmid=22335797}}</ref>


== SGLT2 inhibitors for diabetes ==
== SGLT2 inhibitors for diabetes ==
{{Main|Gliflozin}}
{{Main|SGLT2 inhibitor}}
[[SGLT2 inhibitor]]s 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]].<ref name="HaasEckstein2014">{{cite journal | vauthors = Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD | title = Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin | journal = Nutrition & Diabetes | volume = 4 | issue = 11 | pages = e143 | year = 2014 | pmid = 25365416 | doi = 10.1038/nutd.2014.40 | pmc=4259905}}</ref> The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to euglycemic [[ketoacidosis]].<ref>{{cite journal |last1=Rawla |first1=P |last2=Vellipuram |first2=AR |last3=Bandaru |first3=SS |last4=Pradeep Raj |first4=J |title=Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. |journal=Endocrinology, Diabetes & Metabolism Case Reports |date=2017 |volume=2017 |doi=10.1530/EDM-17-0081 |pmid=28924481|pmc=5592704 }}</ref><ref>{{cite web|url=https://www.fda.gov/Drugs/DrugSafety/ucm446845.htm|title=FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood|date=2015-05-15|publisher=[[Food and Drug Administration]], USA}}</ref> Other side effects of gliflozins include increased risk of Fournier gangrene.<ref>{{cite web|url=https://www.jwatch.org/fw115387/2019/05/07/diabetes-drug-class-associated-with-fournier-gangrene|title=SGLT2 Inhibitors Associated with Fournier Gangrene|publisher=[[Jwatch.org]]|access-date=2019-05-06}}</ref> and (generally mild) [[genital infection]]s such as [[candidal vulvovaginitis]]<ref>{{cite web|url=http://www.diabetes.co.uk/diabetes-medication/sglt2-inhibitors.html|title=SGLT2 Inhibitors (Gliflozins)|publisher=[[Diabetes.co.uk]]|access-date=2015-05-19}}</ref>.
[[SGLT2 inhibitor]]s are also called gliflozins or flozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of [[type 2 diabetes]]. Gliflozins enhance glycemic control as well as reduce [[Human body weight|body weight]] and systolic and diastolic [[blood pressure]].<ref name="HaasEckstein2014">{{cite journal | vauthors = Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD | title = Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin | journal = Nutrition & Diabetes | volume = 4 | issue = 11 | pages = e143 | year = 2014 | pmid = 25365416 | doi = 10.1038/nutd.2014.40 | pmc=4259905}}</ref> The gliflozins [[canagliflozin]], [[dapagliflozin]], and [[empagliflozin]] may lead to euglycemic [[ketoacidosis]].<ref>{{cite journal |last1=Rawla |first1=P |last2=Vellipuram |first2=AR |last3=Bandaru |first3=SS |last4=Pradeep Raj |first4=J |title=Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. |journal=Endocrinology, Diabetes & Metabolism Case Reports |date=2017 |volume=2017 |doi=10.1530/EDM-17-0081 |pmid=28924481|pmc=5592704 }}</ref><ref>{{cite web|url=https://www.fda.gov/Drugs/DrugSafety/ucm446845.htm|title=FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood|date=2015-05-15|publisher=[[Food and Drug Administration]], USA}}</ref> Other side effects of gliflozins include increased risk of Fournier gangrene<ref>{{cite web|url=https://www.jwatch.org/fw115387/2019/05/07/diabetes-drug-class-associated-with-fournier-gangrene|title=SGLT2 Inhibitors Associated with Fournier Gangrene|publisher=[[Jwatch.org]]|access-date=2019-05-06}}</ref> and of (generally mild) [[Reproductive system disease#Infections|genital infection]]s such as [[Vaginal yeast infection|candidal vulvovaginitis]].<ref>{{cite web|url=http://www.diabetes.co.uk/diabetes-medication/sglt2-inhibitors.html|title=SGLT2 Inhibitors (Gliflozins)|publisher=[[Diabetes.co.uk]]|access-date=2015-05-19}}</ref>


== Clinical significance ==
== Clinical significance ==


Mutations in this gene are also associated with [[renal glycosuria]].<ref name="pmid16518345">{{cite journal | vauthors = Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J | title = Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting | journal = Kidney International | volume = 69 | issue = 5 | pages = 852–5 | date = Mar 2006 | pmid = 16518345 | doi = 10.1038/sj.ki.5000194 | doi-access = free }}</ref>
Mutations in this gene are also associated with [[renal glycosuria]].<ref name="pmid16518345">{{cite journal | vauthors = Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J | title = Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting | journal = Kidney International | volume = 69 | issue = 5 | pages = 852–5 | date = Mar 2006 | pmid = 16518345 | doi = 10.1038/sj.ki.5000194 | doi-access = free }}</ref>

== Model organisms ==

{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Slc5a2'' knockout mouse phenotype
|-
! Characteristic!! Phenotype

|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#C40000"|Abnormal<ref name="Indirect calorimetry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/indirect-calorimetry/ |title=Indirect calorimetry data for Slc5a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/salmonella-challenge/ |title=''Salmonella'' infection data for Slc5a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MASE/citrobacter-challenge/ |title=''Citrobacter'' infection data for Slc5a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 | s2cid = 85911512 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of SLC5A2 function. A conditional [[knockout mouse]] line, called ''Slc5a2<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Slc5a2 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4363573 |title=Mouse Genome Informatics}}</ref> 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.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a | doi-access = free }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 | s2cid = 18872015 | doi-access = free }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty two tests were carried out on homozygous [[mutant]] mice and one significant abnormality was observed: males displayed increased drinking behaviour.<ref name="mgp_reference" />


== See also ==
== See also ==

* [[SGLT]] Family
* [[SGLT]] Family
* [[Discovery and development of gliflozins]]
* [[Discovery and development of gliflozins]]
*[[Phlorizin]] - a competitive inhibitor of [[SLC5A1|SGLT1]] and [[SGLT2]]
* [[Phlorizin]] — a competitive inhibitor of [[SLC5A1|SGLT1]] and [[SGLT2]]


== References ==
== References ==

Latest revision as of 22:52, 6 April 2024

SLC5A2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSLC5A2, SGLT2, solute carrier family 5 member 2
External IDsOMIM: 182381; MGI: 2181411; HomoloGene: 2289; GeneCards: SLC5A2; OMA:SLC5A2 - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 7: 127.86 – 127.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[6] SGLT2 is located in the early proximal tubule, and is responsible for reabsorption of 80-90% of the glucose filtered by the kidney glomerulus.[7] Most of the remaining glucose absorption is by sodium/glucose cotransporter 1 (SGLT1) in more distal sections of the proximal tubule.[8]

SGLT2 inhibitors for diabetes[edit]

Main article: SGLT2 inhibitor

SGLT2 inhibitors are also called gliflozins or flozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of type 2 diabetes. Gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure.[9] The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to euglycemic ketoacidosis.[10][11] Other side effects of gliflozins include increased risk of Fournier gangrene[12] and of (generally mild) genital infections such as candidal vulvovaginitis.[13]

Clinical significance[edit]

Mutations in this gene are also associated with renal glycosuria.[14]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140675 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030781 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".
  7. ^ Bonora BM, Avogaro A, Fadini GP (2020). "Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13: 161–174. doi:10.2147/DMSO.S233538. PMC 6982447. PMID 32021362.
  8. ^ Vallon V, Thomson SC (2012). "Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney". Annual Review of Physiology. 74: 351–375. doi:10.1146/annurev-physiol-020911-153333. PMC 3807782. PMID 22335797.
  9. ^ 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. PMC 4259905. PMID 25365416.
  10. ^ Rawla, P; Vellipuram, AR; Bandaru, SS; Pradeep Raj, J (2017). "Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma". Endocrinology, Diabetes & Metabolism Case Reports. 2017. doi:10.1530/EDM-17-0081. PMC 5592704. PMID 28924481.
  11. ^ "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.
  12. ^ "SGLT2 Inhibitors Associated with Fournier Gangrene". Jwatch.org. Retrieved 2019-05-06.
  13. ^ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
  14. ^ 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.

Further reading[edit]

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