Sodium-glucose transport proteins: Difference between revisions

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{{protein
{{infobox protein
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 1
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 1
| caption =  
| caption =  
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| width =  
| width =  
| HGNCid = 11036
| HGNCid = 11036
| Symbol = SLC5A1
| Symbol = [[SLC5A1]]
| AltSymbols = SGLT1
| AltSymbols = SGLT1
| EntrezGene = 6523
| EntrezGene = 6523
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 2
| Name = solute carrier family 5 (sodium/glucose cotransporter), member 2
| caption =  
| caption =  
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| width =  
| width =  
| HGNCid = 11037
| HGNCid = 11037
| Symbol = SLC5A2
| Symbol = [[SLC5A2]]
| AltSymbols = SGLT2
| AltSymbols = SGLT2
| EntrezGene = 6524
| EntrezGene = 6524
Line 37: Line 37:
| LocusSupplementaryData =  
| 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 is excreted in urine ([[glucosuria]]) because SGLT are saturated with the filtered glucose. Glucose is never secreted by a healthy [[Proximal convoluted tubule|nephron]].


{{SI}}
== Types ==
 
 
==Overview==
'''Sodium-dependent glucose cotrasporter 1''' are a family of [[glucose transporter]] found in the intestinal [[mucosa]] of the [[small intestine]] (SGLT1) and the [[proximal tubule]] of the [[nephron]] (SGLT2 and SGLT1). They contribute to [[renal glucose reabsorption]].


==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>
SGLT1 and SGLT2 are members of the SLC5A gene family.


{| class="wikitable"
{| class="wikitable" style="text-align:center"
| '''Gene''' || '''Location'''<ref>Wright EM, Hirayama BA, Loo DF. (2007) "Active sugar transport in health and disease", J Intern Med, 261:32–43</ref> || '''Co-transport ratio and % of glucose reabsorption'''<ref>Wright EM. (2001) "Renal Na+-glucose cotransporters", Am J Physiol Renal Physiol, 280:F10–F18</ref>  
! 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 = J. Intern. Med. | volume = 261 | issue = 1 | pages = 32–43 |date=January 2007 | pmid = 17222166 | doi = 10.1111/j.1365-2796.2006.01746.x | url = | issn = }}</ref>!! Na<sup>+</sup>:Glucose<br/>Co-transport ratio !!  Contribution to glucose<br/>reabsorption (%)<ref name="pmid11133510">{{cite journal | author = Wright EM | title = Renal Na(+)-glucose cotransporters | journal = Am. J. Physiol. Renal Physiol. | volume = 280 | issue = 1 | pages = F10–8 |date=January 2001 | pmid = 11133510 | doi = | url = | issn = }}</ref>
  |-  
  |-  
  | SGLT1 || Located in the S3 segment of the proximal tubule. || Has a 2Na<sup>+</sup>:1Glucose co-transport ratio and is responsible for 2% of glucose reabsorption
  | ''[[SLC5A1]]''  || '''S'''odium/'''GL'''ucose<br/>co'''T'''ransporter '''1''' || SGLT1 || S3 segment || 2:1 || 10
  |-  
  |-  
  | [[SGLT2|Sodium-glucose co-transporter 2]]  || Is predominately located in the S1 and S2 segments of the proximal tubule. || Has a 1Na<sup>+</sup>:1Glucose co-transport ratio and is responsible for 98% of glucose reabsorption.
  | ''[[SLC5A2]]''  || '''S'''odium/'''GL'''ucose<br/>co'''T'''ransporter '''2''' || SGLT2 || predominantly in the<br/>S1 and S2 segments || 1:1 || 90
|}
|}


Including SGLT1 and SGLT2, there are total seven 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</ref>.
== 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]]|accessdate=2015-05-19}}</ref> are used in the treatment of [[type 2 diabetes]]. Examples include [[dapagliflozin]] (Farxiga in US, Forxiga in EU), [[canagliflozin]] (Invokana) and [[empagliflozin]] (Jardiance).
 
== 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>


==Functions==
[[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 Arch. | volume = 447 | issue = 5 | pages = 510–8 |date=February 2004 | pmid = 12748858 | doi = 10.1007/s00424-003-1063-6 | url = | issn = | 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 | author = Boyd CA | title = Facts, fantasies and fun in epithelial physiology | journal = Exp. Physiol. | volume = 93 | issue = 3 | pages = 303–14 |date=March 2008 | pmid = 18192340 | doi = 10.1113/expphysiol.2007.037523 | url = | issn = | 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. }}</ref>
These proteins use the energy from a downhill sodium gradient to transport [[glucose]] across the [[apical]] membrane against an uphill glucose gradient. Therefore, these co-transporters are an example of [[secondary active transport]]. (The GLUT uniporters then transport the glucose across the basolateral membrane, into the [[peritubular capillaries]].)


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


==References==
== References ==
<references/>
{{Reflist}}


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


{{Ion pumps}}
{{Ion pumps}}
{{Membrane transport proteins}}
{{Membrane transport proteins|bg|bg0}}
 


{{WH}}
[[Category:Solute carrier family]]
{{WS}}

Revision as of 19:06, 10 November 2017

solute carrier family 5 (sodium/glucose cotransporter), member 1
Identifiers
SymbolSLC5A1
Alt. symbolsSGLT1
Entrez6523
HUGO11036
OMIM182380
RefSeqNM_000343
UniProtP13866
Other data
LocusChr. 22 q13.1
solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
SymbolSLC5A2
Alt. symbolsSGLT2
Entrez6524
HUGO11037
OMIM182381
RefSeqNM_003041
UniProtP31639
Other data
LocusChr. 16 p11.2
solute carrier family 5 (low affinity glucose cotransporter), member four
Identifiers
SymbolSLC5A4
Alt. symbolsSGLT3, SAAT1, DJ90G24.4
Entrez6527
HUGO11039
RefSeqNM_014227
UniProtQ9NY91
Other data
LocusChr. 22 q12.1-12.3

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 PCT and SGLT1 in 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 PCT, via SGLT2). If the plasma glucose concentration is too high (hyperglycemia), glucose is excreted in urine (glucosuria) because SGLT are saturated with the filtered glucose. Glucose is never secreted by a healthy nephron.

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.[1]

Gene Protein Acronym Tissue distribution
in proximal tubule[2]		 Na+:Glucose
Co-transport ratio		 Contribution to glucose
reabsorption (%)[3]
SLC5A1 Sodium/GLucose
coTransporter 1		 SGLT1 S3 segment 2:1 10
SLC5A2 Sodium/GLucose
coTransporter 2		 SGLT2 predominantly in the
S1 and S2 segments		 1:1 90

SGLT2 inhibitors for diabetes

Main article: Gliflozin

SGLT2 inhibitors, also called gliflozins,[4] are used in the treatment of type 2 diabetes. Examples include dapagliflozin (Farxiga in US, Forxiga in EU), canagliflozin (Invokana) and empagliflozin (Jardiance).

Function

Firstly, an Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule cell uses 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 symporters.

History

In August 1960, in Prague, Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.[5]

Crane's discovery of cotransport was the first-ever proposal of flux coupling in biology.[6][7]

See also

References

  1. ↑ Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509
  2. ↑ Wright EM, Hirayama BA, Loo DF (January 2007). "Active sugar transport in health and disease". J. Intern. Med. 261 (1): 32–43. doi:10.1111/j.1365-2796.2006.01746.x. PMID 17222166.
  3. ↑ Wright EM (January 2001). "Renal Na(+)-glucose cotransporters". Am. J. Physiol. Renal Physiol. 280 (1): F10–8. PMID 11133510.
  4. ↑ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
  5. ↑ Miller D, Bihler I (1961). "The restrictions on possible mechanisms of intestinal transport of sugars". In Kleinzeller A. Kotyk A. Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Czech Academy of Sciences & Academic Press. pp. 439–449.
  6. ↑ Wright EM, Turk E (February 2004). "The sodium/glucose cotransport family SLC5". Pflugers Arch. 447 (5): 510–8. doi:10.1007/s00424-003-1063-6. PMID 12748858. 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.
  7. ↑ Boyd CA (March 2008). "Facts, fantasies and fun in epithelial physiology". Exp. Physiol. 93 (3): 303–14. doi:10.1113/expphysiol.2007.037523. PMID 18192340. p. 304. “the insight from this time that remains in all current text books is the notion of Robert Crane published originally as an appendix to a symposium paper published in 1960 (Crane et al. 1960). The key point here was 'flux coupling', the 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.

External links

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