Acylhydrazones Contribute to Serum Glucose Homeostasis Through Dual Physiological Targets

Author(s): Marisa Jadna Silva Frederico, Allisson Jhonatan Gomes Castro, Alessandra Mascarello, Camila Pires Mendes, Virginia Dermachi Kappel, Taisa Regina Stumpf, Paulo Cesar Leal, Ricardo Jose Nunes, Rosendo Augusto Yunes, Fatima Regina Mena Barreto Silva

Journal Name: Current Topics in Medicinal Chemistry

Volume 12 , Issue 19 , 2012

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In this study the in vivo and in vitro antidiabetic effects of four acylhydrazone derivatives were investigated in rats. The secretagogue action, oral glucose tolerance, insulinogenic index and mechanism of action of these acylhydrazones in relation to calcium uptake in pancreatic islets were studied. Also, the insulinomimetic effect on glycemia in diabetic rats was verified. Of the acylhydrazones studied, 1 and 4 were able to increase glucose tolerance in an acute timecourse. A powerful secretagogue effect was exhibited by 1 and glibenclamide with an insulinogenic index around 3.9 and 1.3-fold higher than that of the hyperglycemic group, respectively. Moreover, an acute and dose-dependent effect of glibenclamide and 1 on calcium uptake in pancreatic islets was observed. The rapid stimulatory effect of 1 on calcium uptake seems to be mediated, at least in part, by ATP-dependent K+ channels (K+-ATP) since the stimulatory effect of 1 was similar to that observed for glibenclamide but was not potentiated by sulphonylurea. Furthermore, both extracellular and calcium from stocks mediate the signal transduction of stimulatory effect of 1 on calcium uptake which may contribute to insulin secretion. In addition, the insulinomimetic effect of 1 was evidenced through the level of serum glucose lowering in alloxan-induced diabetic rats. Also, 1 induced a significant increase in glycogen content in vivo and glucose uptake in soleus muscle in vitro. The results of this study indicate dual physiological targets for the acylhydrazone 1, i.e., pancreatic islets and skeletal muscle, as a result of insulin secretagogue and insulinomimetic action.

Keywords: Acylhydrazones, calcium, insulinomimetic, glucose, glycemia, pancreas, secretagogue, skeletal muscle, oral glucose tolerance, diabetic rats, in vitro antidiabetic.

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Article Details

Year: 2012
Published on: 18 January, 2013
Page: [2049 - 2058]
Pages: 10
DOI: 10.2174/1568026611212190003
Price: $65

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