View source for Sodium-glucose transport proteins

{{infobox protein
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 1
| caption = 
| image = 
| width = 
| HGNCid = 11036
| Symbol = [[SLC5A1]]
| AltSymbols = SGLT1
| EntrezGene = 6523
| OMIM = 182380
| RefSeq = NM_000343
| UniProt = P13866
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 13.1
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 2
| caption = 
| image = 
| width = 
| HGNCid = 11037
| Symbol = [[SLC5A2]]
| AltSymbols = SGLT2
| EntrezGene = 6524
| OMIM = 182381
| RefSeq = NM_003041
| UniProt = P31639
| PDB = 
| ECnumber = 
| Chromosome = 16
| Arm = p
| Band = 11.2
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = solute carrier family 5 (low affinity glucose cotransporter), member four
| caption = 
| image = 
| width = 
| HGNCid = 11039
| Symbol = [[SLC5A4]]
| AltSymbols = SGLT3, SAAT1, DJ90G24.4
| EntrezGene = 6527
| OMIM = 
| RefSeq = NM_014227
| UniProt = Q9NY91
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 12.1-12.3
| LocusSupplementaryData = 
}}
'''Sodium-dependent glucose cotransporters''' (or '''sodium-glucose linked transporter''', '''SGLT''') are a family of [[glucose transporter]] found in the intestinal [[mucosa]] ([[enterocytes]]) of the [[small intestine]] (SGLT1) and the [[proximal tubule]] of the [[nephron]] ([[SGLT2]] in [[Proximal convoluted tubule|PCT]] and SGLT1 in [[Proximal straight tubule|PST]]). They contribute to [[renal glucose reabsorption]]. In the kidneys, 100% of the filtered glucose in the [[glomerulus]] has to be reabsorbed along the nephron (98% in [[Proximal convoluted tubule|PCT]], via SGLT2). If the plasma glucose concentration is too high ([[hyperglycemia]]), glucose passes into the urine ([[glucosuria]]) because SGLT are saturated with the filtered glucose. 

== Types ==

The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family.  In addition to SGLT1 and SGLT2, there are five other members in the human protein family SLC5A, several of which may also be sodium-glucose transporters.<ref>[http://www.ensembl.org/Homo_sapiens/familyview?family=ENSF00000000509 Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509<!-- Bot generated title -->]</ref>

{| class="wikitable" style="text-align:center"
! Gene !! Protein !! Acronym !! Tissue distribution<br/>in proximal tubule<ref name="pmid17222166">{{cite journal | vauthors = Wright EM, Hirayama BA, Loo DF | title = Active sugar transport in health and disease | journal = Journal of Internal Medicine | volume = 261 | issue = 1 | pages = 32–43 | date = January 2007 | pmid = 17222166 | doi = 10.1111/j.1365-2796.2006.01746.x | s2cid = 44399123 | doi-access = free }}</ref>!! Na<sup>+</sup>:Glucose<br/>Co-transport ratio !!  Contribution to glucose<br/>reabsorption (%)<ref name="pmid11133510">{{cite journal | vauthors = Wright EM | title = Renal Na(+)-glucose cotransporters | journal = American Journal of Physiology. Renal Physiology | volume = 280 | issue = 1 | pages = F10–8 | date = January 2001 | pmid = 11133510 | doi = 10.1152/ajprenal.2001.280.1.F10 }}</ref>
 |- 
 | ''[[SLC5A1]]''  || '''S'''odium/'''GL'''ucose<br/>co'''T'''ransporter '''1''' || SGLT1 || S3 segment || 2:1 || 10
 |- 
 | ''[[SLC5A2]]''  || '''S'''odium/'''GL'''ucose<br/>co'''T'''ransporter '''2''' || SGLT2 || predominantly in the<br/>S1 and S2 segments || 1:1 || 90
|}

== SGLT2 inhibitors for diabetes ==
{{Main|Gliflozin}}
SGLT2 inhibitors, also called ''gliflozins'',<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> are used in the treatment of [[type 2 diabetes]].  SGLT2 is only found in kidney tubules and in conjunction with SGLT1 resorbs glucose into the blood from the forming urine. By inhibiting SGLT2, and not targeting SGLT1, glucose is excreted which in turn lowers blood glucose levels. Examples include [[dapagliflozin]] (Farxiga in US, Forxiga in EU), [[canagliflozin]] (Invokana) and [[empagliflozin]] (Jardiance). Certain SGLT2 inhibitors have shown to reduce mortality in type 2 diabetes.<ref>{{cite journal | vauthors = Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE | display-authors = 6 | title = Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes | journal = The New England Journal of Medicine | volume = 373 | issue = 22 | pages = 2117–28 | date = November 2015 | pmid = 26378978 | doi = 10.1056/NEJMoa1504720 | hdl = 11573/894529 | hdl-access = free }}</ref> The safety and efficacy of SGLT2 inhibitors have not been established in patients with [[type 1 diabetes]], and FDA has not approved them for use in these patients.<ref>{{Cite journal|last=Research|first=Center for Drug Evaluation and|date=2018-12-28|title=Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors|url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/sodium-glucose-cotransporter-2-sglt2-inhibitors|journal=FDA|language=en}}</ref>

== Function ==
Firstly, an [[Na+/K+ ATPase]] pump on the [[Cell membrane#Membrane polarity|basolateral]] membrane of the proximal tubule cell uses [[Adenosine triphosphate|ATP]] molecules to move 3 sodium ions outward into the blood, while bringing in 2 potassium ions. This action creates a downhill sodium ion gradient from the outside to the inside of the [[proximal tubule]] cell (that is, in comparison to both the blood and the tubule itself).

The SGLT proteins use the energy from this downhill sodium ion gradient created by the ATPase pump to transport [[glucose]] across the [[apical membrane]], against an uphill glucose gradient. These co-transporters are an example of [[secondary active transport]]. Members of the GLUT family of glucose [[uniporters]] then transport the glucose across the basolateral membrane, and into the [[peritubular capillaries]]. Because sodium and glucose are moved in the same direction across the membrane, SGLT1 and SGLT2 are known as [[symporter]]s.

== History ==

In August 1960, in Prague, [[Robert K. Crane]] presented for the first time his discovery of the sodium-glucose [[Co-transport|cotransport]] as the mechanism for intestinal glucose absorption.<ref>{{cite book|title=Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960|editor=Kleinzeller A. Kotyk A|publisher=[[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]] & Academic Press|chapter = The restrictions on possible mechanisms of intestinal transport of sugars| vauthors = Miller D, Bihler I | pages = 439–449 | year = 1961 }}</ref>

[[Robert K. Crane|Crane]]'s discovery of cotransport was the first-ever proposal of flux coupling in biology.<ref name="pmid12748858">{{cite journal | vauthors = Wright EM, Turk E | title = The sodium/glucose cotransport family SLC5 | journal = Pflugers Archiv | volume = 447 | issue = 5 | pages = 510–8 | date = February 2004 | pmid = 12748858 | doi = 10.1007/s00424-003-1063-6 | s2cid = 41985805 | quote = [[Robert K. Crane|Crane]] in 1961 was the first to formulate the cotransport concept to explain active transport [7]. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type. }}</ref><ref name="pmid18192340">{{cite journal | vauthors = Boyd CA | title = Facts, fantasies and fun in epithelial physiology | journal = Experimental Physiology | volume = 93 | issue = 3 | pages = 303–14 | date = March 2008 | pmid = 18192340 | doi = 10.1113/expphysiol.2007.037523 | s2cid = 41086034 | quote = p. 304. “the insight from this time that remains in all current text books is the notion of [[Robert K. Crane|Robert Crane]] published originally as an appendix to a symposium paper published in 1960 ([[Robert K. Crane|Crane]] et al. 1960). The key point here was 'flux coupling', the [[Co-transport|cotransport]] of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter. | doi-access = free }}</ref>

== See also ==
* [[Co-transport|Cotransport]]
* [[Cotransporter]]
* [[Glucose-galactose malabsorption]]
* [[Renal sodium reabsorption]]
* [[Discovery and development of SGLT-2 inhibitors]]

== References ==
{{Reflist|30em}}

== External links ==
* {{MeshName|Sodium-Glucose+Transport+Proteins}}

{{Ion pumps}}
{{Membrane transport proteins|bg|bg0}}
{{Sodium-glucose transporter modulators}}

[[Category:Solute carrier family]]