Abstract: The diabetic state is known to induce oxidative stress in its
mechanism, which in turn is responsible for the complications of diabetes
mellitus (DM). Recently, we found that Zn(II) complexes have in vitro
insulinomimetic and in vivo blood glucose-lowering activities. During our
study on the development of new Zn(II) complexes with antioxidative ligands
involving L-cysteine, L-cysteine-methylester, and N-acetyl-L-cysteine (nac), we
found a new (N-acetyl-L-cysteinato)Zn(II) (Zn(nac)) complex by evaluating of
both its in vitro insulinomimetic and in vivo potencies. The
insulinomimetic activity of Zn(nac) with respect to the inhibition of free
fatty acid release in isolated rat adipocytes treated with epinephrine was
higher than that of a well-known insulinomimetic VOSO_{4},
being equivalent to that of ZnSO_{4}. The blood glucose
level of hyperglycemic KK-A^{y} mice with type 2 DM was
reduced by daily intraperitoneal injections of Zn(nac) for 28 days. Their serum
insulin, HbA_{1c}, TCHO, and UN levels were remarkably
decreased, indicating that Zn(nac) improved the insulin resistance of the mice.
The improvement of DM by Zn(nac) was also confirmed by the oral glucose
tolerance test. In conclusion, Zn(nac) complex is proposed to attenuate both
hyperglycemia and hyperinsulinemia in KK-A^{y} mice by
decreasing serum insulin, HbA_{1c}, UN, and TCHO levels.
