Yuen Violet G, Bhanot Sanjay, Battell Mary L, Orvig Chris, McNeill John H
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 2003 Nov;81(11):1049-55. doi: 10.1139/y03-094.
The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 micromol/kg) were selected to produce a glucose-lowering effect in 30% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg.day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60% of fatty animals as compared with 30% for BEOV and 10% for ROS alone. The age-dependent decrease in plasma insulin levels associated with beta-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.
本研究的目的是确定噻唑烷二酮衍生物（罗格列酮（ROS））和钒化合物（双（乙基麦芽酚）氧钒（IV）（BEOV））对长期口服给药的Zucker糖尿病脂肪（ZDF）大鼠的血糖和胰岛素水平是否具有协同或相加作用。在时间点0以及第1、6和18天测定全血钒水平。选择BEOV（0.1 mmol/kg）和ROS（2.8 μmol/kg）的剂量，以使30%的动物产生降糖效果（ED30）。两种药物均每日通过口服灌胃给予，以1%羧甲基纤维素（CMC）为混悬剂，体积为2.5 mL/kg。给予所有大鼠的总体积为5 mL/（kg·天）。与单独使用BEOV的30%和单独使用ROS的10%相比，BEOV和ROS的组合可使60%的肥胖动物的血浆葡萄糖水平降至<9 mmol/L。ZDF大鼠中与β细胞功能衰竭相关的血浆胰岛素水平随年龄的下降在BEOV治疗的肥胖组中未出现。任何治疗对体重均无影响；然而，用BEOV治疗的肥胖组的食物和液体摄入量均显著减少。本研究中没有明显的毒性迹象，也没有死亡。如上所述，BEOV和ROS均能有效降低血浆葡萄糖水平，并且当BEOV和ROS联合使用时至少有相加作用。
