Antihyperglycaemic activity of 2,4:3,5-dibenzylidene-D-xylose-diethyl dithioacetal in diabetic mice

Arie Gruzman, Anna Elgart, Olga Viskind, Hana Billauer, Sharon Dotan, Guy Cohen, Eyal Mishani, Amnon Hoffman, Erol Cerasi, Shlomo Sasson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


We have recently generated lipophilic D-xylose derivatives that increase the rate of glucose uptake in cultured skeletal muscle cells in an AMP-activated protein kinase (AMPK)-dependent manner. The derivative 2,4:3,5-dibenzylidene-D-xylose-diethyl dithioacetal (EH-36) stimulated the rate of glucose transport by increasing the abundance of glucose transporter-4 in the plasma membrane of cultured myotubes. The present study aimed at investigating potential antihyperglycaemic effects of EH-36 in animal models of diabetes. Two animal models were treated subcutaneously with EH-36: streptozotocin-induced diabetes in C57BL/6 mice (a model of insulin-deficient type 1 diabetes), and spontaneously diabetic KKAy mice (Kuo Kondo rats carrying the Ay yellow obese gene; insulin-resistant type 2 diabetes). The in vivo biodistribution of glucose in control and treated mice was followed with the glucose analogue 2-deoxy-2-[18F]-D-glucose; the rate of glucose uptake in excised soleus muscles was measured with [3H]-2-deoxy-D-glucose. Pharmacokinetic parameters were determined by non-compartmental analysis of the in vivo data. The effective blood EH-36 concentration in treated animals was 2 μM. It reduced significantly the blood glucose levels in both types of diabetic mice and also corrected the typical compensatory hyperinsulinaemia of KKAy mice. EH-36 markedly increased glucose transport in vivo into skeletal muscle and heart, but not to adipose tissue. This stimulatory effect was mediated by Thr172-phosphorylation in AMPK. Biochemical tests in treated animals and acute toxicological examinations showed that EH-36 was well tolerated and not toxic to the mice. These findings indicate that EH-36 is a promising prototype molecule for the development of novel antidiabetic drugs.

Original languageAmerican English
Pages (from-to)593-603
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Issue number3
StatePublished - Mar 2012


  • AMPK
  • Antihyperglycaemic drugs
  • D-xylose derivatives
  • Diabetes
  • Glucose transport
  • Hyperglycaemia
  • KKAy mice


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