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

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).
AuthorsSubarna Karmaker, Tapan K Saha, Yutaka Yoshikawa, Hiromu Sakurai
JournalMacromolecular bioscience (Macromol Biosci) Vol. 9 Issue 3 Pg. 279-86 (Mar 10 2009) ISSN: 1616-5195 [Electronic] Germany
PMID18989849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Insulin
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Zinc
Topics
  • Administration, Oral
  • Animals
  • Diabetes Mellitus, Type 2 (drug therapy)
  • Hyperglycemia (drug therapy)
  • Insulin
  • Mice
  • Mice, Inbred Strains
  • Molecular Mimicry
  • Polyglutamic Acid (administration & dosage, analogs & derivatives, therapeutic use)
  • Treatment Outcome
  • Zinc

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