Metallokinetic study of zinc in the blood of normal rats given insulinomimetic zinc(II) complexes and improvement of diabetes mellitus in type 2 diabetic GK rats by their oral administration.

In order to understand the insulinomimetic activity of zinc(II) complexes, we studied the metallokinetic features of zinc in the blood of normal rats given the zinc complexes, bis(maltolato)zinc(II) (Zn(mal)(2)) and bis(6-methylpicolinato)zinc(II) (Zn(6mpa)(2)) by comparing each of them with an ionic form of zinc chloride (ZnCl(2)). The bioavailability of the zinc(II) complexes following oral administration was enhanced to 1.4-1.5-fold that of ZnCl(2) with respect to zinc level. Based on the results of a metallokinetic analysis and administration method in normal rats, we examined the antidiabetic ability of the zinc(II) complexes in GK rats, a model animal of type 2 diabetes mellitus. High blood glucose levels of GK rats were normalized following intraperitoneal injections and oral administration of the zinc(II) complexes, in which the Zn(6mpa)(2) complex was found to be more effective than Zn(mal)(2). The present results are noteworthy, not only due to their potential relevance for clinical application, but also for the development of new zinc(II) complexes.