Oral therapy of L-glutamic acid γ-monohydroxamate-vanadium (2:1) complex:: Improvement of blood glucose profile in different types of diabetic rodents

We report that oral administration of vanadium (+5) combined with L-glutamic acid gamma-monohydroxamate at 1:2 stoichiometry [L-Glu(gamma)HXM center dot VO3-] is highly effective in reducing blood glucose levels (BGLs) in a wide variety of diabetic rodents. In streptozocin-treated rats, a single administration (0.28 mmol/kg body wt) decreased BGL from 490 to 360 mg/dI within I h of administration, keeping this reduced level for additional 22 h, and a daily dose of 0.14 mmol/kg was found optimal. In Zucker diabetic fatty (ZDF) rats, a single dose of 0.14 mmol/kg normalized BGL within 8 It of administration, and maintained normal value for additional two days. In db/db mice, a single L-Glu(gamma)HXM center dot VO3- administration of 0.2 mmol/kg decreased BGL from 500 50 to 240 20 mg/dI at 2 h, but was less effective afterwards. In high-carbohydrate, (CHO)-fed Psammomis obesus, a single oral dose (0.14 mmol/kg) normalized BGL over a period of two days, and a daily dose of 0.07 mmol/kg/d, at the time P obesus was transferred from low- to high-CHO diet, fully arrested the development of hyperglycemia characterizing this diabetic rodent. Finally, we found that the index of toxicity of orally administered L-GLU(gamma)HXM-vanadate in rodents is 5-7 times lower than that of free sodium vanadate.