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钒离子对链脲佐菌素诱导的糖尿病大鼠的胰岛素样作用。

Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats.

作者信息

Sakurai H, Tsuchiya K, Nukatsuka M, Sofue M, Kawada J

机构信息

Faculty of Pharmaceutical Science, University of Tokushima, Japan.

出版信息

J Endocrinol. 1990 Sep;126(3):451-9. doi: 10.1677/joe.0.1260451.

DOI:10.1677/joe.0.1260451
PMID:2170556
Abstract

Recent studies have indicated that the blood glucose level of rats with streptozotocin (STZ)-induced diabetes (type 1) is normalized without an increase in the plasma insulin level by administration of sodium orthovanadate in the drinking water. The mechanism of this insulin-like effect of vanadate is unknown. In this study, we investigated whether vanadyl ion, which is less toxic than vanadate to rats, also has an insulin-like effect in rats with STZ-induced diabetes. When rats with STZ-induced diabetes were given a daily i.p. injection of vanadyl sulphate (9.3 and 4.6 mg vanadium/kg body weight), their blood glucose level decreased from about 22.2 to about 7.2 mmol glucose/l within 2 days and remained low for at least 12 weeks. This treatment did not affect their low plasma insulin level. Quantitative electron spin resonance (ESR) spectrometry showed that most of the vanadium (about 90%) in their tissues was present as a vanadyl form (VO2+). ESR analysis also showed that the vanadyl ion in tissues was bound endogenously with four oxygen ligands from either water or oxyamino acid residues in proteins. Vanadyl sulphate accelerated glucose incorporation into adipocytes of rats, suggesting that the action of vanadyl ion is peripheral. Interestingly, vanadyl sulphate at a high concentration (about 10 mmol/l) was more effective than insulin in enhancing glucose uptake. This study demonstrated that: (1) vanadyl sulphate (+4 oxidation state), like vanadate ion, normalizes the blood glucose levels of rats with STZ-induced diabetes; (2) the action of vanadyl ion is peripheral; and (3) the active form of vanadium for an insulin-like effect may be a vanadyl form, not vanadate.

摘要

最近的研究表明,通过在饮用水中给予原钒酸钠,链脲佐菌素(STZ)诱导的糖尿病(1型)大鼠的血糖水平可恢复正常,而血浆胰岛素水平并未升高。钒酸盐这种类似胰岛素作用的机制尚不清楚。在本研究中,我们调查了毒性比钒酸盐对大鼠更低的氧钒离子在STZ诱导的糖尿病大鼠中是否也具有类似胰岛素的作用。给STZ诱导的糖尿病大鼠每日腹腔注射硫酸氧钒(9.3和4.6毫克钒/千克体重),它们的血糖水平在2天内从约22.2毫摩尔葡萄糖/升降至约7.2毫摩尔葡萄糖/升,并至少在12周内保持较低水平。这种治疗并未影响其较低的血浆胰岛素水平。定量电子自旋共振(ESR)光谱分析表明,它们组织中的大部分钒(约90%)以氧钒形式(VO2+)存在。ESR分析还表明,组织中的氧钒离子与来自水或蛋白质中氧氨基酸残基的四个氧配体发生内源性结合。硫酸氧钒加速了葡萄糖掺入大鼠脂肪细胞,表明氧钒离子的作用是外周性的。有趣的是,高浓度(约10毫摩尔/升)的硫酸氧钒在增强葡萄糖摄取方面比胰岛素更有效。本研究表明:(1)硫酸氧钒(+4氧化态)与钒酸盐离子一样,可使STZ诱导的糖尿病大鼠的血糖水平恢复正常;(2)氧钒离子的作用是外周性的;(3)产生类似胰岛素作用的钒的活性形式可能是氧钒形式,而非钒酸盐。

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