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

Gruzman A, Elgart A, Viskind O, Billauer H, Dotan S, Cohen G, Mishani E, Hoffman A, Cerasi E, Sasson S - J. Cell. Mol. Med. (2012)

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.

View Article: PubMed Central - PubMed

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

EH-36 activates AMPK in soleus muscles of STZ-C57BL/6 and KKAy diabetic mice. STZ-C57BL/6 (A, B) and KKAy diabetic mice (C, D) were treated with EH-36 or oil as described in the Figure 2A legend. Soleus muscles were isolated from the mice on day 5 and processed for AMPK and pThr172AMPK Western blot analysis as described under ‘Materials and methods‘. AICAR (4 mM) was added for 30 min. to soleus muscles isolated from untreated animals. (A) and (C) show representative Western blots; (B) and (D) give the summary of band densities of 3 independent experiments (open bars: control mice, black bars: EH-36 treated mice). Mean ± S.E.M., n = 3, *P < 0.05 in comparison with respective oil controls.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3822934&req=5

fig06: EH-36 activates AMPK in soleus muscles of STZ-C57BL/6 and KKAy diabetic mice. STZ-C57BL/6 (A, B) and KKAy diabetic mice (C, D) were treated with EH-36 or oil as described in the Figure 2A legend. Soleus muscles were isolated from the mice on day 5 and processed for AMPK and pThr172AMPK Western blot analysis as described under ‘Materials and methods‘. AICAR (4 mM) was added for 30 min. to soleus muscles isolated from untreated animals. (A) and (C) show representative Western blots; (B) and (D) give the summary of band densities of 3 independent experiments (open bars: control mice, black bars: EH-36 treated mice). Mean ± S.E.M., n = 3, *P < 0.05 in comparison with respective oil controls.

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 [6]. 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).


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

Gruzman A, Elgart A, Viskind O, Billauer H, Dotan S, Cohen G, Mishani E, Hoffman A, Cerasi E, Sasson S - J. Cell. Mol. Med. (2012)

EH-36 activates AMPK in soleus muscles of STZ-C57BL/6 and KKAy diabetic mice. STZ-C57BL/6 (A, B) and KKAy diabetic mice (C, D) were treated with EH-36 or oil as described in the Figure 2A legend. Soleus muscles were isolated from the mice on day 5 and processed for AMPK and pThr172AMPK Western blot analysis as described under ‘Materials and methods‘. AICAR (4 mM) was added for 30 min. to soleus muscles isolated from untreated animals. (A) and (C) show representative Western blots; (B) and (D) give the summary of band densities of 3 independent experiments (open bars: control mice, black bars: EH-36 treated mice). Mean ± S.E.M., n = 3, *P < 0.05 in comparison with respective oil controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822934&req=5

fig06: EH-36 activates AMPK in soleus muscles of STZ-C57BL/6 and KKAy diabetic mice. STZ-C57BL/6 (A, B) and KKAy diabetic mice (C, D) were treated with EH-36 or oil as described in the Figure 2A legend. Soleus muscles were isolated from the mice on day 5 and processed for AMPK and pThr172AMPK Western blot analysis as described under ‘Materials and methods‘. AICAR (4 mM) was added for 30 min. to soleus muscles isolated from untreated animals. (A) and (C) show representative Western blots; (B) and (D) give the summary of band densities of 3 independent experiments (open bars: control mice, black bars: EH-36 treated mice). Mean ± S.E.M., n = 3, *P < 0.05 in comparison with respective oil controls.
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 [6]. 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).

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.

View Article: PubMed Central - PubMed

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