GLUCOSE-LOWERING EFFECTS OF A NEW ORGANIC VANADIUM COMPLEX, BIS(MALTOLATO)OXOVANADIUM(IV)

被引:109
作者
YUEN, VG
ORVIG, C
MCNEILL, JH
机构
[1] UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,DIV PHARMACOL & TOXICOL,2146 E MALL,VANCOUVER V6T 1Z3,BC,CANADA
[2] UNIV BRITISH COLUMBIA,FAC SCI,DEPT CHEM,VANCOUVER V6T 1Z3,BC,CANADA
关键词
BIS(MALTOLATO)OXOVANADIUM(IV); STREPTOZOTOCIN-INDUCED DIABETES; DIABETES TREATMENT;
D O I
10.1139/y93-041
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:263 / 269
页数:7
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