Antihyperglycaemic activity of 2,4:3,5-dibenzylidene-D-xylose-diethyl dithioacetal in diabetic mice.
Bottom Line: The effective blood EH-36 concentration in treated animals was 2 μM.This stimulatory effect was mediated by Thr(172) -phosphorylation in AMPK.These findings indicate that EH-36 is a promising prototype molecule for the development of novel antidiabetic drugs.
Affiliation: Department of Pharmacology, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.Show MeSH
Related in: MedlinePlus
Mentions: We have previously shown that EH-36 in vitro induces translocation of GLUT-4 to the plasma membrane of L6 myotubes in an AMPK-dependent manner . To investigate whether EH-36 operates by this mechanism also in vivo, we treated STZ-C57BL/6 and KKAy mice with EH-36 or oil for 4 days, excised their soleus muscles and determined the extent of Thr172 phosphorylation in AMPK. AICAR, the pharmacological activator of AMPK (added at 4 mM for 30 min. to muscles isolated from naive mice) served as a positive control. Figure 6A–D depicts that Thr172-AMPK phosphorylation was 1.85- and 1.76-fold higher in muscles isolated from EH-36 treated STZ-C57BL/6 and KKAy mice, respectively, in comparison with the respective oil-treated controls. The total muscle content of AMPK was not altered. Of note, the level of AMPK phosphorylation in the liver of both types of mice remained unaltered following EH-36 treatment (data not shown).
Affiliation: Department of Pharmacology, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.