Acute and chronic oral administration of bis(maltolato)oxovanadium(IV) in Zucker diabetic fatty (ZDF) rats

This is a preliminary study in which both acute and chronic oral administra tion of bis(maltolato)oxovanadium (IV) (BMOV) was examined in the Zucker di abetic fatty (ZDF) rat, an animal model that develops overt hyperglycemia i n the presence of hyperinsulinemia followed by beta-cell depletion. At 9-10 weeks of age, in the presence of hyperglycemia, hyperinsulinemia and hyper lipidemia, an acute oral gavage dose response was conducted to determine gl ucose-lowering properties of BMOV, time of response and effect of BMOV on p lasma insulin levels. Doses of BMOV greater than 0.2 mmol/kg resulted in pl asma glucose levels of less than 9 mmol/l. The highest dose administered (0 .8 mmol/kg) significantly reduced plasma insulin (initial: 2.83 +/- 0.2, fi nal: 1.23 +/- 0.09 mmol/l, P < 0.05) and plasma triglyceride (initial: 4.94 +/- 0.33, final: 1.55 +/- 0.07 mmol/l, P < 0.05) levels. At 15 weeks of ag e, in the presence of hyperglycemia, hyperlipidemia and normal insulin leve ls, BMOV was administered orally in the drinking water for a 10-week period to determine the effect of treatment on glucose, insulin and lipid levels. BMOV treatment significantly reduced plasma glucose levels (final BMOV-tre ated: 13.25 +/- 1.43, untreated: 28.71 +/- 0.6 mmol/l, P < 0.05) and effect ively preserved pancreatic beta-cell function. These data suggest a role fo r BMOV as a therapeutic agent in non-insulin-dependent diabetes mellitus th rough improvement in glucose homeostasis and preservation of insulin reserv es. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.