Willsky G R, Goldfine A B, Kostyniak P J, McNeill J H, Yang L Q, Khan H R, Crans D C
Toxicology Research Center, SUNY at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA.
J Inorg Biochem. 2001 May;85(1):33-42. doi: 10.1016/s0162-0134(00)00226-9.
Vanadyl sulfate (VOSO(4)) was given orally to 16 subjects with type 2 diabetes mellitus for 6 weeks at a dose of 25, 50, or 100 mg vanadium (V) daily [Goldfine et al., Metabolism 49 (2000) 1-12]. Elemental V was determined by graphite furnace atomic absorption spectrometry (GFAAS). There was no correlation of V in serum with clinical response, determined by reduction of mean fasting blood glucose or increased insulin sensitivity during euglycemic clamp. To investigate the effect of administering a coordinated V, plasma glucose levels were determined in streptozotocin (STZ)-induced diabetic rats treated with the salt (VOSO(4)) or the coordinated V compound bis(maltolato)oxovandium(IV) (abbreviated as VO(malto)(2)) administered by intraperitoneal (i.p.) injection. There was no relationship of blood V concentration with plasma glucose levels in the animals treated with VOSO(4), similar to our human diabetic patients. However, with VO(malto)(2) treatment, animals with low plasma glucose tended to have high blood V. To determine if V binding to serum proteins could diminish biologically active serum V, binding of both VOSO(4) and VO(malto)(2) to human serum albumin (HSA), human apoTransferrin (apoHTf) and pig immunoglobulin (IgG) was studied with EPR spectroscopy. Both VOSO(4) and VO(malto)(2) bound to HSA and apoHTf forming different V-protein complexes, while neither V compound bound to the IgG. VOSO(4) and VO(malto)(2) showed differences when levels of plasma glucose and blood V in diabetic rodents were compared, and in the formation of V-protein complexes with abundant serum proteins. These data suggest that binding of V compounds to ligands in blood, such as proteins, may affect the available pool of V for biological effects.
给16名2型糖尿病患者口服硫酸氧钒（VOSO₄），剂量为每日25、50或100毫克钒（V），持续6周[Goldfine等人，《新陈代谢》49（2000）1 - 12]。通过石墨炉原子吸收光谱法（GFAAS）测定元素V。血清中的V与临床反应无相关性，临床反应通过空腹平均血糖降低或正常血糖钳夹期间胰岛素敏感性增加来确定。为了研究给予配位V的效果，在用盐（VOSO₄）或通过腹腔注射给予配位V化合物双（麦芽醇根）氧钒（IV）（简称为VO（麦芽醇）₂）治疗的链脲佐菌素（STZ）诱导的糖尿病大鼠中测定血浆葡萄糖水平。与我们的人类糖尿病患者相似，在用VOSO₄治疗的动物中，血液V浓度与血浆葡萄糖水平无关。然而，用VO（麦芽醇）₂治疗时，血浆葡萄糖水平低的动物血液V往往较高。为了确定V与血清蛋白的结合是否会减少具有生物活性的血清V，用电子顺磁共振光谱法研究了VOSO₄和VO（麦芽醇）₂与人血清白蛋白（HSA）、人脱铁转铁蛋白（脱铁HTf）和猪免疫球蛋白（IgG）的结合。VOSO₄和VO（麦芽醇）₂都与HSA和脱铁HTf结合形成不同的V - 蛋白质复合物，而两种V化合物都不与IgG结合。当比较糖尿病啮齿动物的血浆葡萄糖和血液V水平以及与丰富血清蛋白形成V - 蛋白质复合物时，VOSO₄和VO（麦芽醇）₂表现出差异。这些数据表明，V化合物与血液中的配体（如蛋白质）结合可能会影响具有生物学效应的V的可用池。
