This is a preliminary study in which both acute and chronic
oral administration of
bis(maltolato)oxovanadium (IV) (BMOV) was examined in the Zucker diabetic fatty (ZDF) rat, an animal model that develops overt
hyperglycemia in the presence of
hyperinsulinemia followed by beta-cell depletion. At 9-10 weeks of age, in the presence of
hyperglycemia,
hyperinsulinemia and
hyperlipidemia, an acute oral gavage dose response was conducted to determine
glucose-lowering properties of BMOV, time of response and effect of BMOV on plasma
insulin levels. Doses of BMOV greater than 0.2 mmol/kg resulted in plasma
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, final: 1.23+/-0.09 nmol/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 age, in the presence of
hyperglycemia,
hyperlipidemia and normal
insulin levels, 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-treated: 13.25+/-1.43, untreated: 28.71+/-0.6 mmol/l, P<0.05) and effectively preserved pancreatic beta-cell function. These data suggest a role for BMOV as a therapeutic agent in
non-insulin-dependent diabetes mellitus through improvement in
glucose homeostasis and preservation of
insulin reserves.