钠-葡萄糖协同转运蛋白2

钠-葡萄糖协同转运蛋白2
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	7VSI、7YNK、7YNJ
識別號
别名	SLC5A2；, SGLT2, solute carrier family 5 member 2
外部ID	OMIM：182381 MGI：2181411 HomoloGene：2289 GeneCards：SLC5A2
相關疾病
	renal glycosuria
為以下藥物的標靶
	卡納格列淨、达格列净、恩格列淨、sergliflozin etabonate
基因位置（人类）
染色体	16號染色體
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
基因本體
分子功能	• low-affinity glucose:sodium symporter activity; • symporter activity; • transporter activity; • glucose:sodium symporter activity; • transmembrane transporter activity;
細胞組分	• integral component of membrane; • 细胞膜; • 外排體; • 膜; • integral component of plasma membrane;
生物學過程	• carbohydrate transport; • ion transport; • glucose transmembrane transport; • sodium ion transport; • transmembrane transport; • hexose transmembrane transport; • transport; • 碳水化合物代謝;
	Sources:Amigo / QuickGO
直系同源
	6524
	246787
	ENSG00000140675
	ENSMUSG00000030781
	P31639
	Q923I7
	NM_003041
	NM_133254
	NP_003032
	NP_573517
	維基數據
檢視/編輯人類	檢視/編輯小鼠

钠-葡萄糖协同转运蛋白2（英語：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]（溶質載體家族5成員2）基因編碼的蛋白質^[10]。

功能

SGLT2屬於鈉依賴型葡萄糖共同運輸蛋白，是和鈉濃度有關的葡萄糖共同運輸蛋白。SGLT2是腎臟內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]。

大部份SGLT2都是位於近端腎小管細胞中S1段和S2段的刷狀薄膜，負責將腎臟中90%的葡萄糖重新吸收，繼而促進葡萄糖穿過腎臟細胞，再吸收到血液中^[12]^[13]。

作用

對健康人士而言，幾乎所有已過濾的葡萄糖都會被SGLTs重新吸收到近端腎小管 (約90％被SGLT2吸收，其餘10％被SGLT1吸收)，然後返回到血液中。當血糖低於某一水平(即是腎糖水平)，腎臟會吸收葡萄糖，因此尿液中幾乎不會含有糖份^[14]^[12]。

SGLT2和二型糖尿病

至於糖尿病患者，其血糖水平已超過一般的腎糖水平，令葡萄糖必須通過尿液排出體外^[14]。在二型糖尿病患者體內， SGLT2有可能過於活躍，導致腎臟重新吸收過多葡萄糖^[15]^[16]。

抑制SGLT2

抑制SGLT2可減少近端腎小管重新吸收葡萄糖至血液的份量，增加尿糖排泄量、熱量流失和滲透性利尿。因此，抑制SGLT2對血糖、體重和血壓，均有改善作用^[17]^[18]^[19]^[20]。

抑制SGLT2在糖尿病及相關管理中的重要角色

要妥善管理2型糖尿病，是相當複雜及具挑戰性的。雖然2型糖尿病患者可使用各種治療方法降低血糖，但不少個案採用了這些方法後，仍未必能達致理想的血糖目標。至於療效未如理想的成因，多是因為在治療過程中，出現了副作用，如體重增加、低血糖和胃腸道不適等，因而拖延了治療進度^[21]。

钠-葡萄糖协同转运蛋白2抑制剂（SGLT2抑制劑）能直接針對葡萄糖，且毋需依賴β細胞功能和胰島素抗性機制^[22]^[23]。

目前，醫學界正就SGLT2抑制劑的抑制機制進行臨床研究，期望找出此機制對控制糖尿病患者的血糖、體重、血壓、β細胞功能和胰島素抵抗程度等的成效。此外，醫學界亦正在研究SGLT2抑制劑導致低血糖症、尿道和生殖器感染的風險。

醫學界期望，SGLT2抑製劑可成為治療2型糖尿病(T2D)的另一個重要臨床方案。

認識抑製SGLT2的研發過程 ^[24]

早於在1835年，根皮苷複合物是由法國化學家發現可從蘋果樹的根皮中分離出來，後來被研製成SGLT1抑製劑和SGLT2抑製劑。
動物研究顯示，根皮苷能誘導尿糖排泄，使空腹血糖持續正常水平，和避免餐後高血糖症。
SGLT2抑製劑的效用則與根皮苷相類似，但抑製劑已被合成為更有效和更選擇性針對SGLT2，因此治療效果會更為顯著。

參考資料

^ 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.
^ 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.
^ ^3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000140675 - Ensembl, May 2017
^ ^4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000030781 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 存档副本. [2024-03-15]. （原始内容存档于2024-03-08）.
^ 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.
^ 存档副本. [2024-03-15]. （原始内容存档于2019-12-02）.
^ 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 Gene: solute carrier family 5 (sodium/glucose cotransporter). （原始内容存档于2019-07-01）.
^ ^12.0 ^12.1 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.
^ 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
^ ^14.0 ^14.1 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.
^ 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
^ 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
^ 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.
^ List JF, et al. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 Diabetes. Diabetes Care 2009; 32:650-7.
^ 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.
^ 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.
^ 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.
^ 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
^ 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] 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.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000140675 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 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）.

[pmid8244402-10] 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] Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter). （原始内容存档于2019-07-01）.

[#1-12] 12.0 ^12.1 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

[#2-14] 14.0 ^14.1 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.

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

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