钠-葡萄糖协同转运蛋白2

钠-葡萄糖协同转运蛋白2
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	7VSI、7YNK、7YNJ
识别号
别名	SLC5A2；, SGLT2, solute carrier family 5 member 2
外部ID	OMIM：182381 MGI：2181411 HomoloGene：2289 GeneCards：SLC5A2
相关疾病
	renal glycosuria
为以下药物的标靶
	卡纳格列净、达格列净、恩格列净、sergliflozin etabonate
基因位置（人类）
染色体	16号染色体
终止	31,490,860 bp
基因位置（小鼠）
染色体	小鼠7号染色体
终止	127,871,602 bp
基因本体
分子功能	• low-affinity glucose:sodium symporter activity; • symporter activity; • transporter activity; • glucose:sodium symporter activity; • transmembrane transporter activity;
细胞组分	• integral component of membrane; • 细胞膜; • 外排体; • 膜; • integral component of plasma membrane;
生物学过程	• carbohydrate transport; • ion transport; • glucose transmembrane transport; • sodium ion transport; • transmembrane transport; • hexose transmembrane transport; • transport; • 碳水化合物代谢;
	Sources:Amigo / QuickGO
直系同源
	6524
	246787
	ENSG00000140675
	ENSMUSG00000030781
	P31639
	Q923I7
	NM_003041
	NM_133254
	NP_003032
	NP_573517
	维基数据
查看/编辑人类	查看/编辑小鼠

钠-葡萄糖协同转运蛋白2（英语：sodium/glucose cotransporter 2，SGLT2）又称又称钠-葡萄糖耦联转运体2^[7]、钠糖转运子2^[8]，是由SLC5A2^[9]（溶质载体家族5成员2）基因编码的蛋白质^[10]。

Quick Facts 钠-葡萄糖协同转运蛋白2, 已知的结构 ...

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功能

SGLT2属于钠依赖型葡萄糖共同运输蛋白，是和钠浓度有关的葡萄糖共同运输蛋白。SGLT2是肾脏内主要协同转运蛋白葡萄糖重吸收（英语：reabsorption）的主要协同转运蛋白^[11]。

大部分SGLT2都是位于近端肾小管细胞中S1段和S2段的刷状薄膜，负责将肾脏中90%的葡萄糖重新吸收，继而促进葡萄糖穿过肾脏细胞，再吸收到血液中^[12]^[13]。

作用

对健康人士而言，几乎所有已过滤的葡萄糖都会被SGLTs重新吸收到近端肾小管 (约90％被SGLT2吸收，其余10％被SGLT1吸收)，然后返回到血液中。当血糖低于某一水平(即是肾糖水平)，肾脏会吸收葡萄糖，因此尿液中几乎不会含有糖分^[14]^[12]。

SGLT2和2型糖尿病

至于糖尿病患者，其血糖水平已超过一般的肾糖水平，令葡萄糖必须通过尿液排出体外^[14]。在2型糖尿病患者体内， SGLT2有可能过于活跃，导致肾脏重新吸收过多葡萄糖^[15]^[16]。

抑制SGLT2

抑制SGLT2可减少近端肾小管重新吸收葡萄糖至血液的分量，增加尿糖排泄量、热量流失和渗透性利尿。因此，抑制SGLT2对血糖、体重和血压，均有改善作用^[17]^[18]^[19]^[20]。

抑制SGLT2在糖尿病及相关管理中的重要角色

要妥善管理2型糖尿病，是相当复杂及具挑战性的。虽然2型糖尿病患者可使用各种治疗方法降低血糖，但不少个案采用了这些方法后，仍未必能达致理想的血糖目标。至于疗效未如理想的成因，多是因为在治疗过程中，出现了副作用，如体重增加、低血糖和胃肠道不适等，因而拖延了治疗进度^[21]。

钠-葡萄糖协同转运蛋白2抑制剂（SGLT2抑制剂）能直接针对葡萄糖，且毋需依赖β细胞功能和胰岛素抗性机制^[22]^[23]。

目前，医学界正就SGLT2抑制剂的抑制机制进行临床研究，期望找出此机制对控制糖尿病患者的血糖、体重、血压、β细胞功能和胰岛素抵抗程度等的成效。此外，医学界亦正在研究SGLT2抑制剂导致低血糖症、尿道和生殖器感染的风险。

医学界期望，SGLT2抑制剂可成为治疗2型糖尿病(T2D)的另一个重要临床方案。

认识抑制SGLT2的研发过程 [24]

早于在1835年，根皮苷复合物是由法国化学家发现可从苹果树的根皮中分离出来，后来被研制成SGLT1抑制剂和SGLT2抑制剂。
动物研究显示，根皮苷能诱导尿糖排泄，使空腹血糖持续正常水平，和避免餐后高血糖症。
SGLT2抑制剂的效用则与根皮苷相类似，但抑制剂已被合成为更有效和更选择性针对SGLT2，因此治疗效果会更为显著。

参考资料

[1]
與钠-葡萄糖协同转运蛋白2相關的疾病；在維基數據上查看/編輯參考.
[2]
對Solute carrier family 5 member 2起作用的藥物；在維基數據上查看/編輯參考.
[3]
GRCh38: Ensembl release 89: ENSG00000140675 - Ensembl, May 2017
[4]
GRCm38: Ensembl release 89: ENSMUSG00000030781 - Ensembl, May 2017
[5]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[6]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[7]
存档副本. [2024-03-15]. （原始内容存档于2024-03-08）.
[8]
徐鲁斌,田东丽,陈丽萌.钠糖转运子2抑制剂在糖尿病肾病管球反馈调节中的作用[J].中华肾脏病杂志, 2018, 34(6):5.DOI:10.3760/cma.j.issn.1001-7097.2018.06.015.
[9]
存档副本. [2024-03-15]. （原始内容存档于2019-12-02）.
[10]
Wells RG, Mohandas TK, Hediger MA. Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere. Genomics. Sep 1993, 17 (3): 787–9. PMID 8244402. doi:10.1006/geno.1993.1411.
[11]
Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter). （原始内容存档于2019-07-01）.
[12]
Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin. 2009; 25(3):671-81.
[13]
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications; Diabetic Med. 2010;27:136–142
[14]
Abdul-Ghani et al. SGLT2 inhibition and Type 2 Diabetes. Endocrine Reviews, August 2011, 32(4):515–531 7. Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin. 2009; 25(3):671-81.
[15]
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications; Diabetic Med. 2010;27:136–142
[16]
Rahmoune et.al. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non–insulin-dependent diabetes; Diabetes, Vol. 54, December 2005: 3427-34
[17]
Rosenstock J, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with Type 2 Diabetes. Diabetes Care. 2012.
[18]
List JF, et al. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 Diabetes. Diabetes Care 2009; 32:650-7.
[19]
Wilding JPH, et al. A study of dapagliflozin in patients with Type 2 Diabetes receiving high doses of insulin plus insulin sensitizers. Diabetes Care. 2009; 32:1656-62.
[20]
Zhang L, et al. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes, Obesity and Metabolism. 2010; 12:510-6.
[21]
Nair, S. and Wilding, J. P. H. Sodium Glucose Cotransporter 2 Inhibitors as a New Treatment for Diabetes Mellitus. J Clin Endocrinol Metab. 2010. 95(1):34–42.
[22]
Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: A novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocrine Practice. 2008;14:782-90
[23]
Idris I, Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Diabetes Obes Metab. 2009 Feb; 11(2):79-88.
↑
Ehrenkranz, J. R. L. et al. Phlorizin: a review. Diabetes Metab Res Rev. 2005; 21: 31–38.

[1] [1]
與钠-葡萄糖协同转运蛋白2相關的疾病；在維基數據上查看/編輯參考.

[2] [2]
對Solute carrier family 5 member 2起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] [3]
GRCh38: Ensembl release 89: ENSG00000140675 - Ensembl, May 2017

[refGRCm38Ensembl-4] [4]
GRCm38: Ensembl release 89: ENSMUSG00000030781 - Ensembl, May 2017

[5] [5]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] [6]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[7] [7]
存档副本. [2024-03-15]. （原始内容存档于2024-03-08）.

[8] [8]
徐鲁斌,田东丽,陈丽萌.钠糖转运子2抑制剂在糖尿病肾病管球反馈调节中的作用[J].中华肾脏病杂志, 2018, 34(6):5.DOI:10.3760/cma.j.issn.1001-7097.2018.06.015.

[9] [9]
存档副本. [2024-03-15]. （原始内容存档于2019-12-02）.

[pmid8244402-10] [10]
Wells RG, Mohandas TK, Hediger MA. Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere. Genomics. Sep 1993, 17 (3): 787–9. PMID 8244402. doi:10.1006/geno.1993.1411.

[entrez-11] [11]
Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter). （原始内容存档于2019-07-01）.

[#1-12] [12]
Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin. 2009; 25(3):671-81.

[13] [13]
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications; Diabetic Med. 2010;27:136–142

[#2-14] [14]
Abdul-Ghani et al. SGLT2 inhibition and Type 2 Diabetes. Endocrine Reviews, August 2011, 32(4):515–531 7. Bays H. From victim to ally: the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin. 2009; 25(3):671-81.

[15] [15]
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications; Diabetic Med. 2010;27:136–142

[16] [16]
Rahmoune et.al. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non–insulin-dependent diabetes; Diabetes, Vol. 54, December 2005: 3427-34

[17] [17]
Rosenstock J, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with Type 2 Diabetes. Diabetes Care. 2012.

[18] [18]
List JF, et al. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 Diabetes. Diabetes Care 2009; 32:650-7.

[19] [19]
Wilding JPH, et al. A study of dapagliflozin in patients with Type 2 Diabetes receiving high doses of insulin plus insulin sensitizers. Diabetes Care. 2009; 32:1656-62.

[20] [20]
Zhang L, et al. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes, Obesity and Metabolism. 2010; 12:510-6.

[21] [21]
Nair, S. and Wilding, J. P. H. Sodium Glucose Cotransporter 2 Inhibitors as a New Treatment for Diabetes Mellitus. J Clin Endocrinol Metab. 2010. 95(1):34–42.

[22] [22]
Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: A novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocrine Practice. 2008;14:782-90

[23] [23]
Idris I, Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Diabetes Obes Metab. 2009 Feb; 11(2):79-88.

[24] 
Ehrenkranz, J. R. L. et al. Phlorizin: a review. Diabetes Metab Res Rev. 2005; 21: 31–38.

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