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钒盐作为胰岛素替代品:作用机制,糖尿病研究中的科学与治疗工具

Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research.

作者信息

Sekar N, Li J, Shechter Y

机构信息

Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Crit Rev Biochem Mol Biol. 1996 Dec;31(5-6):339-59. doi: 10.3109/10409239609108721.

Abstract

Vanadium and its compounds exhibit a wide variety of insulin-like effects. In this review, these effects are discussed with respect to the treatment of type I and type II diabetes in animal models, in vitro actions, antineoplastic role, treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s) involved. Newly established CytPTK plays a major role in the bioresponses of vanadium. It has a molecular weight of approximately 53 kDa and is active in the presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers, staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity of protein tyrosine kinases. Our data show that inhibition of PTPase and protein tyrosine kinase activation has a major role in the therapeutic efficacy of vanadium in treating diabetes mellitus.

摘要

钒及其化合物呈现出多种类胰岛素效应。在本综述中,将从动物模型中对I型和II型糖尿病的治疗、体外作用、抗肿瘤作用、对胰岛素依赖型糖尿病(IDDM)和非胰岛素依赖型糖尿病(NIDDM)患者的治疗、毒性以及可能涉及的机制等方面来讨论这些效应。新发现的细胞蛋白酪氨酸激酶(CytPTK)在钒的生物反应中起主要作用。它的分子量约为53 kDa,在Co2+存在而非Mn2+存在时具有活性。在蛋白酪氨酸激酶阻滞剂中,发现星形孢菌素是CytPTK的有效抑制剂,但对胰岛素受体酪氨酸激酶(InsRTK)的抑制作用较弱。钒抑制蛋白酪氨酸磷酸酶(PTPase)活性,进而增强蛋白酪氨酸激酶的活性。我们的数据表明,抑制PTPase和激活蛋白酪氨酸激酶在钒治疗糖尿病的疗效中起主要作用。

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