In developing new insulin-mimetic vanadyl complexes with various ligands including biodegradable polymers, we prepared and characterized three VO(g-pga) complexes in solution and evaluated their in vitro insulin-mimetic activities and in vivo anti-diabetic effects in streptozotocin (STZ)-induced type 1 like diabetic mice (STZ-mice). All three VO(g-pga) complexes normalized the hyperglycemia in STZ-mice within 14 d when administered orally at doses of 10 mg V kg–1 body mass for 28 d. In addition, the impaired glucose tolerance, elevated HbA1c levels and metabolic syndromes were significantly improved in VO(g-pga) complexes-treated STZ-mice relative to those administrated with saline and VS. Vanadium was distributed in the tissues examined in the following decreasing order: bones, liver, muscles, spleen, heart, kidneys, brain, lungs and pancreas. VO(g-pga) complexes in which -pga having average molecular weight 480 - 4700 kDa are promising oral therapeutic agents for the treatment of type 1 diabetic animals.
Key words: Vanadyl-poly(g-glutamic acid) complex, STZ-mice, drug delivery system, diabetes, hyperglycemia.
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