Sodium-glucose transport proteins

solute carrier family 5 (sodium/glucose cotransporter), member 2
solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
Symbol	SLC5A2
Alt. symbols	SGLT2
NCBI gene	6524
HGNC	11037
OMIM	182381
RefSeq	NM_003041
UniProt	P31639
Other data
Locus	Chr. 16 p11.2
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

solute carrier family 5 (sodium/glucose cotransporter), member 1
solute carrier family 5 (sodium/glucose cotransporter), member 1
Identifiers
Symbol	SLC5A1
Alt. symbols	SGLT1
NCBI gene	6523
HGNC	11036
OMIM	182380
RefSeq	NM_000343
UniProt	P13866
Other data
Locus	Chr. 22 q13.1
Structures
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Structures	Swiss-model
Domains	InterPro

solute carrier family 5 (low affinity glucose cotransporter), member 4

Identifiers

Symbol

SLC5A4

Alt. symbols

SGLT3, SAAT1, DJ90G24.4

Other data

Chr. 22 q12.1-12.3

Search for
Structures	Swiss-model
Domains	InterPro

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

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 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]

References

^ Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509
^ 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.
^ Wright EM (January 2001). "Renal Na(+)-glucose cotransporters". Am. J. Physiol. Renal Physiol. 280 (1): F10–8. PMID 11133510.
^ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
^ Miller D, Bihler I (1961). "The restrictions on possible mechanisms of intestinal transport of sugars". In Kleinzeller A. Kotyk A (ed.). Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Czech Academy of Sciences & Academic Press. pp. 439–449.
^ 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.
^ 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

Sodium-Glucose+Transport+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[1] Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509

[pmid17222166-2] 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.

[pmid11133510-3] 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 (ed.). Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Czech Academy of Sciences & Academic Press. pp. 439–449.

[pmid12748858-6] 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.

[pmid18192340-7] 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.

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