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 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.
Yuen
V G
VG
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Vera
E
E
Battell
M L
ML
Li
W M
WM
McNeill
J H
JH
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity; D011753:Pyrones / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker / Q000097:blood* / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000008:administration & dosage* / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011753:Pyrones; D014280:Triglycerides; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates