Khandelwal R L, Pugazhenthi S
Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Mol Cell Biochem. 1995;153(1-2):87-94. doi: 10.1007/BF01075922.
The insulin-mimetic action of vanadate is well established but the exact mechanism by which it exerts this effect is still not clearly understood. The role of insulin in the regulation of hepatic glycogen metabolizing and lipogenic enzymes is well known. In our study, we have, therefore, examined the effects of vanadate on these hepatic enzymes using four different models of diabetic and insulin-resistant animals. Vanadate normalized the blood glucose levels in all animal models. In streptozotocin-induced diabetic rats, the amount of liver glycogen and the activities of the active-form of glycogen synthase, both active and inactive-forms of phosphorylase, and lipogenic enzymes like glucose 6-phosphate dehydrogenase and malic enzyme were decreased and vanadate treatment normalized all of these to near normal levels. The other three animal models (db/db mouse, sucrose-fed rats and fa/fa obese Zucker rats) were characterized by hyperinsulinemia, hypertriglyceridemia, increases in activities of lipogenic enzymes, and marginal changes in glycogen metabolizing enzymes. Vanadate treatment brought all of these values towards normal levels. It should be noted that vanadate shows differential effects in the modulation of lipogenic enzymes activities in type I and type II diabetic animals. It increases the activities of lipogenic enzymes in streptozotocin-induced diabetic animals and prevents the evaluation of activities of these enzymes in hyperinsulinemic animals. The insulin-stimulated phosphorylation of insulin receptor beta subunit and its tyrosine kinase activity was increased in streptozotocin-induced diabetic rats after treatment with vanadate. Our results support the view that insulin receptor is one of the sites involved in the insulin-mimetic actions of vanadate.
钒酸盐的胰岛素模拟作用已得到充分证实，但其发挥这种作用的确切机制仍不清楚。胰岛素在调节肝糖原代谢酶和脂肪生成酶方面的作用是众所周知的。因此，在我们的研究中，我们使用四种不同的糖尿病和胰岛素抵抗动物模型，研究了钒酸盐对这些肝酶的影响。钒酸盐使所有动物模型的血糖水平恢复正常。在链脲佐菌素诱导的糖尿病大鼠中，肝糖原含量、糖原合酶活性形式的活性、磷酸化酶活性和非活性形式的活性以及葡萄糖6 - 磷酸脱氢酶和苹果酸酶等脂肪生成酶的活性均降低，而钒酸盐治疗使所有这些指标恢复到接近正常水平。其他三种动物模型（db/db小鼠、蔗糖喂养的大鼠和fa/fa肥胖 Zucker 大鼠）的特征是高胰岛素血症、高甘油三酯血症、脂肪生成酶活性增加以及糖原代谢酶的轻微变化。钒酸盐治疗使所有这些值趋于正常水平。应该注意的是，钒酸盐在调节 I 型和 II 型糖尿病动物的脂肪生成酶活性方面表现出不同的作用。它增加链脲佐菌素诱导的糖尿病动物中脂肪生成酶的活性，并阻止高胰岛素血症动物中这些酶活性的评估。在用钒酸盐治疗后，链脲佐菌素诱导的糖尿病大鼠中胰岛素刺激的胰岛素受体β亚基磷酸化及其酪氨酸激酶活性增加。我们的结果支持这样一种观点，即胰岛素受体是参与钒酸盐胰岛素模拟作用的位点之一。
