钠-葡萄糖协同转运蛋白2 - Wikiwand
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钠-葡萄糖协同转运蛋白2

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SLC5A2
识别号
别名SLC5A2;SGLT2、​solute carrier family 5 member 2
外部IDOMIM182381 MGI2181411 HomoloGene:2289 GeneCardsSLC5A2
相关疾病
renal glycosuria[1]
为以下药物的标靶
卡纳格列净、​达格列净、​恩格列净、​sergliflozin etabonate[2]
直系同源
物种人类小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_003041、NR_130783、XM_006721072、XM_024450402

NM_133254

蛋白序列

NP_003032、XP_006721135、XP_024306170

NP_573517

基因位置​(UCSC)Chr 16: 31.48 – 31.49 Mbn/a
PubMed​查找[3][4]
维基数据
检视/编辑 人类检视/编辑 小鼠

钠-葡萄糖协同转运蛋白2(SGLT2)是由SLC5A2(溶质载体家族5成员2)基因编码的蛋白质[5]

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[6]

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[7][8]

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[9][10]

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[11]。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[12][13]

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[14][15][16][17]

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,但不少病例采用了这些方法后,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[18]

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[19][20]

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

  • 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。

参考数据

  1. ^ 与SLC5A2相关的疾病;在维基数据上查看/编辑参考. 
  2. ^ 对Solute carrier family 5 member 2起作用的药物;在维基数据上查看/编辑参考. 
  3. ^ Human PubMed Reference:. 
  4. ^ Mouse PubMed Reference:. 
  5. ^ 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. 
  6. ^ Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter). 
  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.
  8. ^ 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
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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
  13. ^ 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
  14. ^ 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.
  15. ^ List JF, et al. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 Diabetes. Diabetes Care 2009; 32:650-7.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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
  20. ^ 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.
  21. ^ Ehrenkranz, J. R. L. et al. Phlorizin: a review. Diabetes Metab Res Rev. 2005; 21: 31–38.
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钠-葡萄糖协同转运蛋白2
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