Goldwaser I, Gefel D, Gershonov E, Fridkin M, Shechter Y
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
J Inorg Biochem. 2000 May 30;80(1-2):21-5. doi: 10.1016/s0162-0134(00)00035-0.
Most mammalian cells contain vanadium at a concentration of about 20 nM, the bulk of which is probably in the reduced vanadyl (+4) form. Although this trace element is essential and should be present in the diet in minute quantities, no known physiological role for vanadium has been found thus far. In the late 1970s the vanadate ion was shown to act as an efficient inhibitor of Na+,K+-ATPase as well as of other related phosphohydrolases. In 1980 vanadium was reported to mimic the metabolic effects of insulin in rat adipocytes. During the last decade, vanadium has been found to act in an insulin-like manner in all three main target tissues of the hormone, namely skeletal muscles, adipose, and liver. Subsequent studies revealed that the action of vanadium salts is mediated through insulin-receptor independent alternative pathway(s). The investigation of the antidiabetic potency of vanadium soon ensued. Vanadium therapy was shown to normalize blood glucose levels in STZ-rats and to cure many hyperglycemia-related deficiencies. Therapeutic effects of vanadium were then demonstrated in type II diabetic rodents, which do not respond to exogenously administered insulin. Finally, clinical studies indicated encouraging beneficial effects. A major obstacle, however, is overcoming vanadium toxicity. Recently, several organically chelated vanadium compounds were found more potent and less toxic than vanadium salts in vivo. Such a newly discovered organic chelator of vanadium is described in this review.
大多数哺乳动物细胞中钒的浓度约为20纳摩尔，其中大部分可能呈还原态的钒离子（+4价）形式。尽管这种微量元素是必需的，且在饮食中应微量存在，但迄今为止尚未发现钒有任何已知的生理作用。20世纪70年代末，钒酸盐离子被证明是Na +，K + -ATP酶以及其他相关磷酸水解酶的有效抑制剂。1980年，据报道钒在大鼠脂肪细胞中可模拟胰岛素的代谢作用。在过去十年中，已发现钒在该激素的所有三个主要靶组织，即骨骼肌、脂肪和肝脏中，均以胰岛素样方式发挥作用。随后的研究表明，钒盐的作用是通过不依赖胰岛素受体的替代途径介导的。对钒的抗糖尿病效力的研究很快就展开了。钒疗法被证明可使链脲佐菌素诱导的糖尿病大鼠的血糖水平恢复正常，并治愈许多与高血糖相关的缺陷。随后在对外源性胰岛素无反应的II型糖尿病啮齿动物中证实了钒的治疗效果。最后，临床研究显示出令人鼓舞的有益效果。然而，一个主要障碍是克服钒的毒性。最近，发现几种有机螯合钒化合物在体内比钒盐更有效且毒性更小。本文综述了这种新发现的钒有机螯合剂。
