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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