International Journal of Medical Sciences

Impact factor
2.399

23 October 2017

ISSN 1449-1907 News feeds of published articles

My Manuscript | My Account

Journal of Genomics now in PubMed/PubMed Central. Submit manuscript...

Journal of Biomedicinenew

Theranostics

Journal of Cancer

Oncomedicine

International Journal of Biological Sciences

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Med Sci 2007; 4(3):131-139. doi:10.7150/ijms.4.131

Research Paper

Thioglycosides as inhibitors of hSGLT1 and hSGLT2: Potential therapeutic agents for the control of hyperglycemia in diabetes

Francisco Castaneda1, Antje Burse2, Wilhelm Boland2, Rolf K-H. Kinne1

1. Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute of Molecular Physiology, Dortmund, Germany
2. Max Planck Institute for Chemical Ecology, Dortmund, Germany

Abstract

The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by SGLT1 or SGLT2, represents a promising therapeutic approach. Therefore, the aim of the present study was to evaluate the effect of thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected Chinese hamster ovary (CHO) cells expressing human SGLT1 and SGLT2 were used. The inhibitory effect of thioglycosides was assessed in transport studies and membrane potential measurements, using α-methyl-glucoside uptake and fluorescence resonance energy transfer, respectively. We found that some thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically, thioglycoside I (phenyl-1'-thio-β-D-glucopyranoside) inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1'-thio-β-D-galacto-pyranoside) had a pronounced inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating competitive inhibition as the mechanism of action. Therefore, these thioglycosides represent promising therapeutic agents for the control of hyperglycemia in patients with diabetes.

Keywords: Thioglycoside, sodium-dependent glucose transport, α-methyl-glucoside uptake, fluorescence resonance energy transfer, diabetes, hyperglycemia

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Castaneda F, Burse A, Boland W, Kinne RKH. Thioglycosides as inhibitors of hSGLT1 and hSGLT2: Potential therapeutic agents for the control of hyperglycemia in diabetes. Int J Med Sci 2007; 4(3):131-139. doi:10.7150/ijms.4.131. Available from http://www.medsci.org/v04p0131.htm