The pharmacology of the insulinomimetic effect of zinc complexes.

Abstract

In developing new insulinomimetic zinc(II) complexes with different coordination structures and with a blood glucose-lowering effect to treat type 2 diabetic animals, we found a potent bis(maltolato)zinc(ll) complex, Zn(mal)(2). Using the complex as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(mal)(2) and its related complexes in respect to the inhibition of free fatty acids (FFA) release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine (adrenaline), and hypoglycemic activity. Among the compounds tested, a new Zn(II) complex with allixin that was isolated from garlic, bis(allixinato)Zn(II), Zn(alx)(2), was found to exhibit the highest insulin-mimetic and hypoglycemic activities in type 2 KK-A(y) diabetic mice. On the basis of the results, Zn(alx)(2), complex was proposed to be a potent candidate for the treatment of type 2 diabetes.