Sodium-glucose transport proteins

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solute carrier family 5 (sodium/glucose cotransporter), member 1
Symbol SLC5A1
Alt. symbols SGLT1
Entrez 6523
HUGO 11036
OMIM 182380
RefSeq NM_000343
UniProt P13866
Other data
Locus Chr. 22 q13.1
solute carrier family 5 (sodium/glucose cotransporter), member 2
Symbol SLC5A2
Alt. symbols SGLT2
Entrez 6524
HUGO 11037
OMIM 182381
RefSeq NM_003041
UniProt P31639
Other data
Locus Chr. 16 p11.2
solute carrier family 5 (low affinity glucose cotransporter), member 4
Symbol SLC5A4
Alt. symbols SGLT3, SAAT1, DJ90G24.4
Entrez 6527
HUGO 11039
RefSeq NM_014227
UniProt Q9NY91
Other data
Locus Chr. 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). In case of too high plasma glucose concentration (hyperglycemia), glucose is excreted in urine (glucosuria); because SGLT are saturated with the filtered monosaccharide. Glucose is never secreted by the nephron.


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]
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[edit]

Inhibition of SGLT2 leads to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type II diabetes. Several drug candidates have been developed or are currently undergoing clinical trials, including:[4]

  • Dapagliflozin, approval rejected in 2012 by Food and Drug Administration due to safety concerns however after resubmitting additional clinical data is under review with Dec 12, 2013 as PDUFA Date,[5] but marketed in Europe and Australia. Dapagliflozin was the first SGLT2 approved anywhere in the world in 2011 by the EU.
  • Canagliflozin, approved in the United States and Canada[6]
  • Ipragliflozin (ASP-1941), in Phase III clinical trials[7]
  • Tofogliflozin, in Phase III clinical trials[7]
  • Empagliflozin, approved in the United States[8]
  • Sergliflozin etabonate, discontinued after Phase II trials
  • Remogliflozin etabonate, in phase IIb trials


Firstly, the Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule cell uses ATP to move 3 sodium ions outward into the blood, while bringing in 2 potassium ions. This creates a downhill sodium ion gradient inside the proximal tubule cell in comparison to both the blood and the tubule. 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. 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.) Both SGLT1 and SGLT2 are known as symporters, since both sodium ions and glucose are transported in the same direction across the membrane.

Discovery of sodium-glucose cotransport[edit]

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.[9]

Crane's discovery of cotransport was the first-ever proposal of flux coupling in biology.[10][11]

See also[edit]


  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. ^ InsightPharma (2010). "Diabetes Pipeline: Intense Activity to Meet Unmet Need". p. vii. 
  5. ^ Bristol, AstraZeneca Diabetes Drug Fails to Win FDA Backing, Business Week, January 19, 2012
  6. ^ Invokana, First in New Class of Diabetes Drugs, Approved, MPR, March 29, 2013
  7. ^ a b SGLT2 inhibitor approval race
  8. ^ "FDA approves Jardiance® (empagliflozin) tablets for adults with type 2 diabetes". Boehringer Ingelheim / Eli Lilly and Company. 1 August 2014. Retrieved 5 November 2014. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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[edit]