Antidiabetic Activity of the Orally Effective Vanadyl-Poly (-Glutamic Acid) Complex in Streptozotocin(STZ)-induced Type 1 Diabetic Mice

¹ Department of Chemistry, Colorado State University Fort Collins, CO 80523, USA; Department of Analytical and Bioinorganic Chemistry Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi Yamashina-ku, Kyoto 607-8414, Japan; Department of Chemistry, Jahangirnagar University, Saver, Dhaka 1342, Bangladesh
² Department of Analytical and Bioinorganic Chemistry Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi Yamashina-ku, Kyoto 607-8414, Japan

^* To whom correspondence should be addressed.

	Abstract

Newly synthesized vanadyl-poly(-glutamic acid) complex (VO--PGA) with a VO(O₄) coordination mode was found to have potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that of a solution containing only vanadyl sulfate, VOSO₄. This was the first example of orally active vanadyl complex of -PGA for treating STZ-mice. To better define its efficacy, we examined here the effects of VO--PGA treatment in STZ-mice by oral administration at the dose of 10 mg V/kg body mass for a longer period time than our previous study. The improvement in diabetic states in STZ-mice compared with saline-treated nondiabetic normal Std ddY mice. It was found that the elevated blood glucose levels in STZ-mice significantly decreased after 3 days and sustained the normalized blood glucose level around 180-200 mg/dL (10-11.1 mM) for the last 14 days, which is close to the blood glucose levels 100-200 mg/dL (5.6-11.1 mM) in nondiabetic normal Std ddY mice. The improvement in diabetes was strongly corelated by the improvement in oral glucose tolerance ability, glycosylated hemoglobin (HbA_1c) levels and blood pressure, and serum parameters. The present results confirmed that VO--PGA complex is a promising, orally active insulin-mimetic agent to treat type 1 diabetic mice.

Key Words: vanadyl-poly(-glutamic acid) complex, biodegradable polymer, drug delivery system, diabetes, hyperglycemia, STZ-mice

First published on May 10, 2007, doi:10.1177/0885328207078067

Journal of Biomaterials Applications 2008;22:449.

A more recent version of this article appeared on March 1, 2008
This version was published on November 6, 2007


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