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Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKA y Mice by Poly(γ‐glutamic acid)oxovanadium(IV) Complex
Author(s) -
Karmaker Subarna,
Saha Tapan K.,
Yoshikawa Yutaka,
Sakurai Hiromu
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700132
Subject(s) - hyperinsulinemia , medicine , endocrinology , insulin , in vivo , type 2 diabetes , diabetes mellitus , chemistry , insulin resistance , streptozotocin , pharmacology , biology , microbiology and biotechnology
Recently, we found that poly(γ‐glutamic acid)oxovanadium(IV) complex (VO(γ‐pga)) exhibits a potent antidiabetic activity in streptozotocin (STZ)‐induced type 1 diabetic mice. This result prompted us to examine its ability to treat the type 2 diabetic model KKA y mice with insulin resistance. We studied the in vivo antidiabetic activity of VO(γ‐pga), compared with that of vanadium(IV) oxide sulfate (VS) as control. Both compounds were orally administered at doses of 5–10 mg (0.1–0.2 mmol) V kg −1 body mass to the KKA y mice for 30 days. VO(γ‐pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA 1c level, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia were significantly improved in VO(γ‐pga)‐treated KKA y mice compared with those treated with VS. Based on these observations, VO(γ‐pga) is proposed to be the first orally active oxovanadium(IV)‐polymer complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndrome in animals.