Yuen V G, Pederson R A, Dai S, Orvig C, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 1996 Sep;74(9):1001-9.
The fatty Zucker rat, characterized by obesity, hyperinsulinemia, hyperlipidemia, and mild hyperglycemia, has been suggested as an animal model of non-insulin-dependent diabetes mellitus. The present study examined the chronic dose-dependent effect of bis(maltolato)oxovanadium(IV), a potent insulin mimetic, in this animal model of diabetes. Chronic (6 weeks) oral administration of bis(maltolato)oxovanadium(IV) (0.06 mmol.kg-1.day-1, low dose study) was effective in reducing the hyperinsulinemia associated with the fatty Zucker rat model (termination insulin: lean, 82.8 +/- 21.6; fatty, 732 +/- 89.4; fatty treated, 336 +/- 126.6 pmol/L; p < 0.05). Pancreatic perfusion data indicated a significant improvement in insulin secretory function in the fatty rats. The dose dependency of this relationship was observed in the high dose study (0.128 mmol.kg-1.day-1 for 14 weeks), wherein bis(maltolato)oxovanadium(IV) treatment restored plasma insulin levels in the fatty rats to lean levels (termination insulin: lean, 199.2 +/- 17.4; fatty 660.6 +/- 12.6; fatty treated, 153.6 +/- 9.6 pmol/L; p < 0.05) and significantly improved insulin response to a glucose challenge. In addition, bis(maltolato)oxovanadium(IV) treatment (high dose study) ameliorated the age-dependent increase in blood pressure observed in fatty Zucker rats (systolic blood pressure: lean, 127 +/- 10; fatty, 176 +/- 5; fatty treated, 156 +/- 9 mmHg (1 mmHg = 133.3 Pa)). These data indicate that chronic oral administration of bis(maltolato)oxovanadium(IV) in the drinking water was effective in reducing hyperinsulinemia, insulin resistance, glucose intolerance, and hypertension in the fatty Zucker rat.
脂肪型 Zucker 大鼠以肥胖、高胰岛素血症、高脂血症和轻度高血糖为特征，已被提议作为非胰岛素依赖型糖尿病的动物模型。本研究在该糖尿病动物模型中检测了双（麦芽醇）氧钒（IV）（一种有效的胰岛素模拟物）的慢性剂量依赖性效应。双（麦芽醇）氧钒（IV）（0.06 mmol·kg⁻¹·天⁻¹，低剂量研究）的慢性（6 周）口服给药有效降低了与脂肪型 Zucker 大鼠模型相关的高胰岛素血症（终止时胰岛素水平：瘦鼠，82.8±21.6；脂肪型大鼠，732±89.4；脂肪型大鼠给药组，336±126.6 pmol/L；p<0.05）。胰腺灌注数据表明脂肪型大鼠的胰岛素分泌功能有显著改善。在高剂量研究（0.128 mmol·kg⁻¹·天⁻¹，持续 14 周）中观察到了这种关系的剂量依赖性，其中双（麦芽醇）氧钒（IV）治疗使脂肪型大鼠的血浆胰岛素水平恢复到瘦鼠水平（终止时胰岛素水平：瘦鼠，199.2±17.4；脂肪型大鼠，660.6±12.6；脂肪型大鼠给药组，153.6±9.6 pmol/L；p<0.05），并显著改善了胰岛素对葡萄糖刺激的反应。此外，双（麦芽醇）氧钒（IV）治疗（高剂量研究）改善了脂肪型 Zucker 大鼠中观察到的随年龄增长的血压升高（收缩压：瘦鼠，127±10；脂肪型大鼠，176±5；脂肪型大鼠给药组，156±9 mmHg（1 mmHg = 133.3 Pa））。这些数据表明，在饮用水中慢性口服双（麦芽醇）氧钒（IV）可有效降低脂肪型 Zucker 大鼠的高胰岛素血症、胰岛素抵抗、葡萄糖不耐受和高血压。
