A Zinc(II)/Poly(γ-glutamic acid) Complex as an Oral Therapeutic for the Treatment of Type-2 Diabetic KKAy Mice

• Published in: Macromolecular bioscience 2009-03, Vol.9 (3), p.279-286
• Main Authors: Karmaker, Subarna, Saha, Tapan K., Yoshikawa, Yutaka, Sakurai, Hiromu
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aminoacid polymers; Animals; antidiabetic effect; Applied sciences; Biological and medical sciences; Diabetes Mellitus, Type 2 - drug therapy; Exact sciences and technology; General pharmacology; Hyperglycemia - drug therapy; Insulin; insulin-mimetic activity; Medical sciences; metabolic syndromes; Mice; Mice, Inbred Strains; Molecular Mimicry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyglutamic Acid - administration & dosage; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - therapeutic use; Synthetic biopolymers; Treatment Outcome; type-2 diabetes; Zinc; zinc(II)/poly(γ-glutamic acid) complex
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.200800190

In developing new insulin‐mimetic zinc(II) complexes with various ligands including a biodegradable polymer, we prepared and characterized a Zn(γ‐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 KKAy mice. The in vitro insulin‐mimetic activity of the Zn(γ‐pga) complex was considerable better than that of ZnSO4. The Zn(γ‐pga) complex normalized the hyperglycemia in KKAy 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 HbA1c levels and metabolic syndromes were significantly improved in Zn(γ‐pga)‐treated KKAy mice relative to those administrated with saline and ZnSO4.