Nagareddy Prabhakara Reddy, Vasudevan Harish, McNeill John H
Division of Pharmacology and Toxicology, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Can J Physiol Pharmacol. 2005 May;83(5):405-11. doi: 10.1139/y05-026.
Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.
使高血糖和高血脂正常化是预防糖尿病诱发心脏功能障碍的一个重要目标。我们的研究基于钨酸钠潜在的抗糖尿病和抗氧化活性,调查了其对链脲佐菌素诱导的(STZ)糖尿病大鼠心脏功能的影响。将雄性Wistar大鼠制成STZ糖尿病模型,然后在其饮用水中加入钨酸钠进行为期9周的治疗。测量大鼠的体重、食物和液体摄入量、血浆葡萄糖、胰岛素、甘油三酯和游离脂肪酸水平。在研究期结束时,进行口服葡萄糖耐量试验(OGTT),并使用离体工作心脏装置评估心脏功能。经钨酸钠治疗的STZ糖尿病大鼠的液体和食物摄入量、血浆葡萄糖、甘油三酯和游离脂肪酸水平显著降低,并且在OGTT中对葡萄糖的耐受性提高,这是由于钨酸钠介导的胰岛素活性增强而非胰岛素水平升高所致。经钨酸钠治疗的糖尿病大鼠的左心室压力上升、收缩速率(+dP/dT)和舒张速率(-dP/dT)均显著改善。除了体重增加率降低外,在经钨酸钠治疗的大鼠中未观察到其他毒性迹象或低血糖发作。本研究扩展了先前关于钨酸钠抗糖尿病活性的观察结果,并且首次报道了其在预防糖尿病性心肌病方面的有益作用。