Poucheret P, Verma S, Grynpas M D, McNeill J H
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Mol Cell Biochem. 1998 Nov;188(1-2):73-80.
We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-term effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanadium compounds. One of these, bismaltolato-oxovanadium IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadium is a phosphatase inhibitor and that vanadium can activate serine/threonine kinases distal to the insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.
1985年我们证明，给链脲佐菌素（STZ）诱导的糖尿病大鼠饮用含钒的水可使升高的血糖恢复正常。随后的研究表明，硫酸氧钒能降低多种糖尿病模型（包括STZ糖尿病大鼠、Zucker肥胖大鼠和Zucker糖尿病肥胖大鼠）中升高的血糖、胆固醇和甘油三酯。长达一年的长期研究表明，给对照大鼠或STZ大鼠服用能降低血糖升高的剂量的硫酸氧钒，未显示出毒性。在胰岛素依赖型糖尿病模型BB糖尿病大鼠中，硫酸氧钒可使胰岛素需求量降低多达75%。硫酸氧钒单次给药或长期给药时口服均有效。腹腔注射给药也有效。我们还能够证明硫酸氧钒在糖尿病动物治疗及停药后具有显著的长期效应。由于硫酸氧钒吸收不佳，我们合成并测试了多种有机钒化合物。其中一种，双麦芽醇氧钒（IV）（BMOV），已显示出作为治疗剂的前景。BMOV的效力比硫酸氧钒高2至3倍，且毒性较小。我们实验室最近的研究表明，钒的作用并非由于食物摄入量减少，而且虽然钒沉积在骨骼中，但似乎不影响骨骼强度或结构。钒的作用机制目前正在研究中。多项研究表明，钒是一种磷酸酶抑制剂，钒可能通过抑制磷酸酶防止去磷酸化，从而激活胰岛素受体下游的丝氨酸/苏氨酸激酶。在糖尿病患者中使用无机钒化合物的短期临床试验前景良好。
