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

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

Tapan Kumar Saha

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, tksaha_ju{at}yahoo.com, Department of Chemistry, Jahangirnagar University Saver Dhaka 1342, Bangladesh

Hiromu Sakurai

Department of Analytical and Bioinorganic Chemistry Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi Yamashina-ku, Kyoto 607-8414, Japan

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, VOSO ₄. 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.

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