Effects of Inorganic Ion Dependent-Correlation between the Insulin-Mimetic Activity and Nitric Oxide Production from Macrophages

Abstract

Nitric oxide (NO) production from macrophages has been proposed to mediate the destruction of islet B-cells. Recently, we found that vanadium suppresses NO production from macrophages in STZ-induced diabetic mice. Then, we examined whether inorganic ions with insulin-mimetic activity such as Hg (II) , Cd (II) , Se (IV) , V (III) , V (IV) , Zn (II) and Mn (II) suppress NO production from macrophages. Dose-dependent inhibitory effects of these elements for NO production were observed, being in the following order: Hg (II) > Cd (II) > Se (IV) > V (III) > V (IV) > Zn (II) > Mn (II) .

To evaluate the insulin-mimetic activity of these ions, we examined the inhibitory effects of FFA release from adipocytes at the concentration of lmM of the ions. The inhibitory activity of FF A release from adipocytes was found to be in the order of Hg (II) > Cd (II) > Se (IV) > V (III) > V (IV) > Zn (II) > Mn (II) .

A correlation between inhibitory activity of FF A release and that of NO production was observed. This finding suggests that insulin-mimetic effects of these ions depend partially on the inhibition of NO production in adipocytes.