title: SGLT inhibitors as new therapeutic tools in the treatment of diabetes.
abstract: 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 .
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany. rolf.kinne@mpi-dortmund.mpg.de
authors.forename: Rolf K H
authors.initials: RK
authors.lastname: Kinne
authors.forename: Francisco
authors.initials: F
authors.lastname: Castaneda
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use*; D010695:Phlorhizin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; D010695:Phlorhizin