Kinne Rolf K H, Castaneda Francisco
Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.
Handb Exp Pharmacol. 2011(203):105-26. doi: 10.1007/978-3-642-17214-4_5.
Recently, the idea has been developed to lower blood glucose blood glucose levels in diabetes by inhibiting sugar reabsorption sugar reabsorption in the kidney kidney . The main target is thereby the early proximal tubule proximal tubule where secondary active transport secondary active transport of the sugar is mediated by the sodium-D: -glucose D-glucose cotransporter SGLT2 SGLT2 . A model substance for the inhibitors inhibitors is the O-glucoside O-glucoside phlorizin phlorizin which inhibits transport transport competitively. Its binding to the transporter involves at least two different domains: an aglucone binding aglucone binding site at the transporter surface, involving extramembranous loops extramembraneous loops , and the sugar binding sugar binding /translocation site buried in a hydrophilic pocket of the transporter. The properties of these binding sites differ between SGLT2 and SGLT1 SGLT1 , which mediates sugar absorption sugar absorption in the intestine intestine . Various O-, C-, N- and S-glucosides have been synthesized with high affinity affinity and high specificity specificity for SGLT2 SGLT2 . Some of these glucosides are in clinical trials clinical trials and have been proven to successfully increase urinary glucose excretion urinary glucose excretion and to decrease blood sugar blood sugar levels without the danger of hypoglycaemia hypoglycaemia during fasting fasting in type 2 diabetes type 2 diabetes .
最近，人们提出了通过抑制肾脏中的糖重吸收来降低糖尿病患者血糖水平的想法。主要靶点是早期近端小管，在那里糖的继发性主动转运由钠 - D - 葡萄糖协同转运蛋白SGLT2介导。抑制剂的一种模型物质是O - 葡萄糖苷根皮苷，它竞争性地抑制转运。它与转运蛋白的结合涉及至少两个不同的结构域：转运蛋白表面的一个苷元结合位点，涉及膜外环，以及埋在转运蛋白亲水口袋中的糖结合/转位位点。这些结合位点的性质在SGLT2和SGLT1之间有所不同，SGLT1介导肠道中的糖吸收。已经合成了各种对SGLT2具有高亲和力和高特异性的O - 、C - 、N - 和S - 葡萄糖苷。其中一些葡萄糖苷正在进行临床试验，并且已被证明能成功增加尿糖排泄并降低血糖水平，在2型糖尿病患者禁食期间不会有低血糖风险。
