Vasudevan Harish, McNeill John H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.
Biometals. 2007 Apr;20(2):129-34. doi: 10.1007/s10534-006-9020-4. Epub 2006 Jun 27.
Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.
糖尿病是一种以血糖水平升高为特征的代谢紊乱疾病。尽管胰岛素和其他药物等传统治疗方法可降低血糖,但仍需要有效的口服药物进行治疗。钒和钨酸盐等微量元素已成功证明可在实验性糖尿病中降低血糖,且慢性并发症极少。我们研究了钴对链脲佐菌素诱导的糖尿病大鼠的降血糖作用。正常大鼠和糖尿病大鼠饮用含3.5 mM氯化钴的水三周,然后饮用含4 mM氯化钴的水四周。每天监测体重和液体摄入量,每周记录两次食物摄入量。在处死前,对动物进行口服葡萄糖耐量试验。与对照组(482±3克)相比,糖尿病大鼠体重显著减轻(357±2克)。钴治疗使体重进一步减轻(290±2克)。尽管在不导致体重减轻的情况下难以确定给药方案,但与未治疗的糖尿病大鼠相比,钴治疗的糖尿病大鼠的食物和液体摄入量显著改善。与糖尿病对照组(29.3±0.9 mM)相比,到第四周时血浆葡萄糖水平显著降低至较低但仍处于高血糖水平(13.6±3.4 mM)。与未治疗的糖尿病大鼠相比,钴治疗的糖尿病大鼠清除葡萄糖负荷的能力增强。钴治疗既不影响正常血糖动物的进食和饮水模式,也不影响其血浆葡萄糖水平,尽管与未治疗的对照组相比体重有所下降。我们得出结论,慢性钴治疗可降低链脲佐菌素诱导的糖尿病大鼠的血浆葡萄糖水平,并提高对葡萄糖的耐受性。