A Zinc(II)/poly(gamma-glutamic acid) complex as an oral therapeutic for the treatment of type-2 diabetic KKAy mice.

In developing new insulin-mimetic zinc(II) complexes with various ligands including a biodegradable polymer, we prepared and characterized a Zn(gamma-pga) complex in solution as well as in solid, and investigated its in vitro insulin-mimetic activity and in vivo antidiabetic effect in type-2 diabetic KKA(y) mice. The in vitro insulin-mimetic activity of the Zn(gamma-pga) complex was considerable better than that of ZnSO(4). The Zn(gamma-pga) complex normalized the hyperglycemia in KKA(y) mice within 21 d when administrated orally at doses of 10-20 mg (0.15-0.31 mmol) Zn per kg body mass for 30 d. In addition, the impaired glucose tolerance, elevated HbA(1c) levels and metabolic syndromes were significantly improved in Zn(gamma-pga)-treated KKA(y) mice relative to those administrated with saline and ZnSO(4).