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SGLT Inhibitors as New Therapeutic Tools in the Treatment of Diabetes

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Book cover Diabetes - Perspectives in Drug Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 203))

Abstract

Recently, the idea has been developed to lower blood glucose levels in diabetes by inhibiting sugar reabsorption in the kidney . The main target is thereby the early proximal tubule where secondary active transport of the sugar is mediated by the sodium-d-glucose cotransporter SGLT2 . A model substance for the inhibitors is the O-glucoside phlorizin which inhibits transport competitively. Its binding to the transporter involves at least two different domains: an aglucone binding site at the transporter surface, involving extramembranous loops , and the sugar binding /translocation site buried in a hydrophilic pocket of the transporter. The properties of these binding sites differ between SGLT2 and SGLT1 , which mediates sugar absorption in the intestine . Various O-, C-, N- and S-glucosides have been synthesized with high affinity and high specificity for SGLT2 . Some of these glucosides are in clinical trials and have been proven to successfully increase urinary glucose excretion and to decrease blood sugar levels without the danger of hypoglycaemia during fasting in type 2 diabetes .

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Acknowledgments

The authors would like to thank Christine Riemer, for her outstanding organizational skill and computer proficiency, as well as her endurance and patience. Without her, the writing of this chapter while travelling between two continents would not have been possible. Also, the enthusiastic and untiring support of the staff of the library of the Max Planck Institute, particularly Christiane Berse and Jürgen Block is gratefully acknowledged. In the analysis of the differences of the aglucone binding site of hSGLT1 and hSGLT2 , Dr. Thorsten Althoff, now at the Max Planck Institute of Biophysics in Frankfurt, Germany, provided essential help.

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  1. Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany

    Rolf K. H. Kinne & Francisco Castaneda

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  1. Rolf K. H. Kinne
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Correspondence to Rolf K. H. Kinne .

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  1. Fakultät Lebenswissenschaften Molekulare Pharmakologie und Toxikologie, Technische Universität Braunschweig, Beethovenstraße 55, 38106, Braunschweig, Germany

    Mathias Schwanstecher

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Kinne, R.K.H., Castaneda, F. (2011). SGLT Inhibitors as New Therapeutic Tools in the Treatment of Diabetes. In: Schwanstecher, M. (eds) Diabetes - Perspectives in Drug Therapy. Handbook of Experimental Pharmacology, vol 203. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17214-4_5

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