偏钒酸钠降低糖尿病小鼠血糖及其对葡萄糖磷酸化的影响

Hypoglycemic effects of sodium metavanadate in diabetic mice and its effect on glucose phosphorylation

目的 通过研究偏钒酸钠对小鼠的血糖及葡萄糖磷酸化关键酶的影响 ,探讨偏钒酸钠降血糖作用的可能机制。方法 将糖尿病小鼠和正常对照小鼠 ,随机分为口服偏钒酸钠组和非口服偏钒酸钠组 ,分别饮用 2 0 0mg/L偏钒酸钠溶液和 80mmol/L的NaCl对照溶液 ,持续 5周。在实验第 0至 5周的每周末 ,对各组小鼠的血糖、肝脏葡萄糖激酶、肌肉己糖激酶以及胰岛素水平进行检测。结果 在给予偏钒酸钠前 ,糖尿病小鼠血糖水平明显高于正常对照组 ,服药 1周后 ,血糖值即由(18 77± 1 2 8)mmol/L下降至 (8 94± 0 94 )mmol/L ,接近正常水平 ;其肝脏葡萄糖激酶和肌肉己糖激酶的活性则显著升高 ,分别由 (1 2 9± 0 6 4 )mIU·min-1·mg-1蛋白质和 (1 93± 0 5 0 )mIU·min-1·mg-1蛋白质上升至 (15 36± 1 5 7)mIU·min-1·mg-1蛋白质和 (18 6 2± 1 71)mIU·min-1·mg-1蛋白质 (P <0 0 1) ;而在服药前后糖尿病小鼠的胰岛素水平差异均无显著性。上述作用在小鼠服药期间始终存在。相关分析显示 ,糖尿病小鼠的血糖水平与葡萄糖激酶和己糖激酶的活性呈显著的负相关性。结论 偏钒酸钠的降血糖作用并不依赖于体内胰岛素水平的增加 ;改善糖尿病小鼠体内不良的葡萄糖磷酸化过程 ,可能是偏钒酸钠降血糖作用的机制之一。

Objective To investigate the effects of sodium metavanadate (SMV) on blood sugar and glucose phosphorylation in mice,and to discuss the possible mechanism of its hypoglycemic effects. Methods Diabetic mice (D) and control mice (V) were randomly allocated to drink SMV (0.2 mg/ml) (CV and DV groups) or NaCl (80 mmol/L) (C and V groups) respectively.The study lasted for 5 weeks.Liver glucokinase,muscle hexokinase,blood glucose and insulin were assayed at the end of each week. Results Blood glucose was higher in the diabetic groups before the administration of SMV,and the blood glucose level of group DV decreased from (18.77±1.28) to (8.94±0.94) mmol/L( P <0.01) after oral administration of SMV for one week.While liver glucokinase increased from (1.29±0.64) to (15.36±1.57) mIU/min/mg protein and muscle hexokinase increased from(1.93±0.50) to (18.62±1.71) mIU/min/mg protein ( P <0.01) respectively.There was no continuous change of these parameters during the later weeks.No significant change of serum insulin was observed in the diabetic mice.There was a remarkable negative correlation of blood glucose level with liver glucokinase and muscle hexokinase levels. Conclusion The hypoglycemic effects of SMV was independent of insulin level.In consideration of the close relations of the activities of liver glucokinase and muscle hexokinase with diabetes,and the improving of impaired glucose phosphorylation in diabetic mice by oral sodium metavanadate,which might be the mechanism of hypoglycemic effects of SMV.