WordNet

a silvery soft waxy metallic element of the alkali metal group; occurs abundantly in natural compounds (especially in salt water); burns with a yellow flame and reacts violently in water; occurs in sea water and in the mineral halite (rock salt) (同)Na, atomic number 11
a monosaccharide sugar that has several forms; an important source of physiological energy

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ソジウム,ナトリウム(金属元素;化学記号はNa)
ブドウ糖

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/14 11:06:25」(JST)

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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.

Types

The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family.

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

Function

Firstly, the Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule, cell actively (requires ATP) transports sodium from this cell into the peritubular capillary. This creates a downhill sodium gradient inside the proximal tubule cell. The SGLT proteins use the energy from this downhill sodium 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 and glucose are transported in the same direction across the membrane.

Discovery of sodium-glucose cotransport

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.^[4]

Crane's discovery of cotransport was the first-ever proposal of flux coupling in biology.^[5]^[6]

References

^ 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.
^ Ensembl release 48: Homo sapiens Ensembl protein family ENSF00000000509
^ 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.
^ 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 US National Library of Medicine Medical Subject Headings (MeSH)

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UpToDate Contents

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1. Chapter 3A：近位尿細管輸送の細胞モデル chapter 3a cell model for proximal transport
2. 糖尿病患者における高血圧治療 treatment of hypertension in patients with diabetes mellitus
3. Chapter 3B：近位尿細管におけるナトリウム輸送能の優越性 chapter 3b primacy of sodium transport in proximal function
4. 消化管の発達に関する概要 overview of the development of the gastrointestinal tract
5. 乳糖不耐症 lactose intolerance

English Journal

Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade.

Weber MA1, Mansfield TA2, Alessi F3, Iqbal N4, Parikh S4, Ptaszynska A2.
Blood pressure.Blood Press.2016 Apr;25(2):93-103. doi: 10.3109/08037051.2015.1116258. Epub 2015 Dec 1.
Hypertension and type 2 diabetes mellitus (T2DM) are risk factors for cardiovascular disease. Dapagliflozin improves glycemic control and systolic blood pressure (SBP) in T2DM patients. This double-blind phase III study evaluated the effects of dapagliflozin on glycemic control and blood pressure in
PMID 26623980

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus.

Davis PN1, Ndefo UA2, Oliver A2.
Journal of pharmacy practice.J Pharm Pract.2016 Apr;29(2):165-71. doi: 10.1177/0897190014566308. Epub 2015 Jan 21.
OBJECTIVE: To review clinical evidence for the efficacy, safety, and tolerability of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2 inhibitor, as monotherapy or in combination with other hypoglycemic agents for the treatment of type 2 diabetes.DATA SOURCES: Literature was iden
PMID 25609661

Intestinal SGLT1 in Metabolic health and Disease.

Lehmann A1, Hornby PJ2.
American journal of physiology. Gastrointestinal and liver physiology.Am J Physiol Gastrointest Liver Physiol.2016 Mar 24:ajpgi.00068.2016. doi: 10.1152/ajpgi.00068.2016. [Epub ahead of print]
The sodium/glucose cotransporter 1 (SGLT1/SLC5A1) is predominantly expressed in the small intestine. It transports glucose and galactose across the apical membrane in a process driven by a sodium gradient created by Na+/K+ATPase. SGLT2 is the major form found in the kidney and SGLT2 selective inhibi
PMID 27012770

Japanese Journal

SGLT阻害薬 (新臨床糖尿病学(上)糖尿病学の最新動向) -- (糖尿病の予防・管理・治療)

池田富貴,綿田裕孝
日本臨床 70(-) (1020(増刊3)), 716-720, 2012-05
NAID 40019325070

Colocalization of GLUT2 glucose transporter, sodium/glucose cotransporter, and γ-glutamyl transpeptidase in rat kidney with double peroxidase immunocytochemistry

CRAMER SC.
Diabetes 41, 766-770, 1992
NAID 30026274095

Related Pictures

★リンクテーブル★

リンク元	「sodium-glucose transport protein」「Na+/グルコース共輸送体」「ナトリウム・グルコース共輸送体」「Na+-glucose cotransporter」「ナトリウム・ブドウ糖共輸送体」
拡張検索	「sodium-glucose cotransporter 1」「sodium-glucose cotransporter 2」
関連記事	「cotransport」「cotransporter」

「sodium-glucose transport protein」

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

solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
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 (sodium/glucose cotransporter), member 1
Identifiers
Symbol	SLC5A1
Alt. symbols	SGLT1
Entrez	6523
HUGO	11036
OMIM	182380
RefSeq	NM_000343
UniProt	P13866
Other data
Locus	Chr. 22 q13.1