Advanced search×

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

Francisco F Castaneda, Antje A Burse, Wilhelm W Boland, and Rolf K-H RK Kinne

Int J Med Sci 4(3):131-9 (2007) PMID 17505558 PMCID 1868657

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 alpha-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-beta-D-glucopyranoside) inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1'-thio-beta-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.

Version: za2963e q8za4 q8zba q8zc1 q8zd7 q8ze2 q8zfb q8zg8
View PDF

Similar articles you may find interesting…

  1. Atomoxetine does not alter cocaine use in cocaine dependent individuals: A double blind randomized trial
    Sharon L Walsh, Lisa S Middleton, and Michelle R Lofwall

    Drug Alcohol Depend 130(1-3):150-157 (2013) PMID 23200303

    Survival analysis revealed no differences in study retention between the two groups, with approximately 56% of subjects completing the 12-week study (Cox analysis χ(2)=.72; p=.40; Hazard Ratio 1.48 [95% CI 0.62-3.39]). GEE analysis of the proportion of urine samples positive for benzoylecgonine, a...
  2. Highly Potent Inhibitors of Quorum Sensing in Staphylococcus aureus Revealed Through a Systematic Synthetic Study of the Group-III Autoinduc...
    Yftah Tal-Gan, Danielle M Stacy, and Helen E Blackwell

    J Am Chem Soc (2013) PMID 23647400

    We seek to expand this set of chemical probes, and report herein the first design, synthesis, and biological testing of AIP-III mimetics. A set of non-native peptides was identified that can inhibit all four of the AgrC receptors (I-IV) with picomolar IC50 values in reporter strains. These analogs a...
  3. Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease.
    Mohan Ganesh Karmarkar, Gouri Pandharinath Hule, and Kadaba Srinivasa Sriprakash

    BMC Nephrol 14(1):101 (2013) PMID 23642030

    Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients....
    PDF not found