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
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Mentions: The effect of EH-36 on blood glucose levels was evaluated following its s.c. injection (10 mg/kg of EH-36, twice a day) to STZ-treated C57BL/6 mice and KKAy diabetic mice. EH-36 demonstrated marked antihyperglycaemic activity: it significantly reduced blood glucose in STZ-treated C57BL/6 mice by 33% and 54% on days 3 and 4 of treatment, respectively, whereas oil treatment (vehicle) had no effect (Fig. 2A). EH-36 was even more effective in KKAy diabetic mice: blood glucose was reduced by 39%, 55% and 60% on days 2, 3 and 4 of treatment, respectively (Fig. 2B). Similar results were observed in these animals when the treatment was extended to 7 days. Yet, normoglycaemia was not attained in the diabetic mice following these 4- and 7 day treatments. In the rest of the experiment the mice were treated with EH-36 for 4 days to minimize the accumulation of oil at the sites of injection and to lower the risk of developing inflammatory reactions. In parallel with the reduction of blood glucose concentration, the KKAy mice, which are usually hyperinsulinaemic, became normoinsulinaemic during this treatment (Fig. 2C). The glucose-lowering effect of EH-36 was not restricted to diabetic animals: Figure 2D shows that it reduced blood glucose also by 20–25% in normoglycaemic control C57BL/6 mice.
Affiliation: Department of Pharmacology, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.