バナジル―ホスホネート関連錯体の in vitro および in vivo インスリン様活性

抄録

Much interest has been focused on the potency of vanadyl (VO) complexes as an orally active antidiabetic agent. Because the numbers of insulinomimetic VO complexes reported to date are still limited, we prepared a new series of VO complexes with ligands containing phosphonate group.

In vitro insulinomimetic activities of the complexes were higher than that of VOSO₄ (VS) in terms of IC₅₀ value, 50% inhibition concentration of VO complex on epinephrine-stimulated free fatty acids (FFA) release from isolated rat adipocytes. Among them, a vanadyl-N-(phosphonomethyl) iminodiacetate (VO (pida)) complex exhibited the highest activity. In in vivo trial, high blood glucose levels of streptozotocin-induced diabetic rats (STZ-rats) were normalized within 7 days after daily oral administrations of the complex, and glucose tolerance of rats was improved. From the results, it was concluded that vanadyl-phosphonate complexes are proposed to be a new candidate for orally active therapeutic of type 1 diabetes mellitus.