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

Macromol Biosci. 2009 Mar 10;9(3):279-86. doi: 10.1002/mabi.200800190.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Hyperglycemia / drug therapy
  • Insulin
  • Mice
  • Mice, Inbred Strains
  • Molecular Mimicry
  • Polyglutamic Acid / administration & dosage
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / therapeutic use
  • Treatment Outcome
  • Zinc*

Substances

  • Insulin
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Zinc