Glucose-lowering effects of a new organic vanadium complex, bis(maltolato)oxovanadium(IV).
Inorganic vanadium has been shown, both in vivo and in vitro, to have insulin-mimetic properties. A new organic vanadium complex, bis(maltolato)oxovanadium(IV) (BMOV), was developed to increase the absorption of vanadium from the gastrointestinal tract, thereby reducing the dose of vanadium necessary to produce glucose-lowering effects. BMOV was administered in the drinking water for 25 weeks to control and streptozotocin-induced diabetic, male Wistar rats. BMOV treatment produced a stable euglycemic state in 70% of diabetic treated animals. The other 30% of the diabetic treated animals demonstrated fluctuations in glucose control over the entire study period. The initial effective dose of BMOV was 0.45 mmol/kg, which decreased to an effective maintenance dose of 0.18 mmol/kg, significantly lower than the dose of inorganic vanadium salts used in previous studies. BMOV treatment did significantly reduce fluid consumption levels in control treated animals after 10 weeks of therapy; however, the food consumption for control treated animals was only intermittently lower than that for controls. Plasma cholesterol and triglyceride levels were normalized with BMOV treatment for all diabetic treated animals, without a concomitant increase in plasma insulin levels. An oral glucose tolerance test demonstrated that glucose homeostasis in control-treated animals occurred at significantly lower plasma insulin levels than in control animals. BMOV effectively produced the glucose-lowering effects at significantly lower dose than previously used for inorganic vanadium salts, without any overt signs of toxicity.
Yuen
V G
VG
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Orvig
C
C
McNeill
J H
JH
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002241:Carbohydrates / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D002241:Carbohydrates; D005223:Fats; D007004:Hypoglycemic Agents; D008055:Lipids; D011753:Pyrones; D014280:Triglycerides; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D002784:Cholesterol