钒（III、IV、V）-氯代二吡啶甲酸盐对链脲佐菌素诱导的糖尿病大鼠肝脏糖酵解和抗氧化状态的影响

Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant status in the liver of STZ-induced diabetic rats.

作者信息

Xie Mingxia, Chen Deliang, Zhang Fang, Willsky Gail R, Crans Debbie C, Ding Wenjun

机构信息

College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

出版信息

J Inorg Biochem. 2014 Jul;136:47-56. doi: 10.1016/j.jinorgbio.2014.03.011. Epub 2014 Mar 31.

DOI:10.1016/j.jinorgbio.2014.03.011

PMID:24747360

Abstract

Vanadium compounds exert various insulin-mimetic and anti-diabetic effects both in vitro and in vivo. Vanadium(III, IV, V)-chlorodipicolinate (Vdipic-Cl) compounds, including H[V(III)(dipic-Cl)2]·5H2O (V3dipic-Cl), V(IV)O(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[V(V)O2(dipic-Cl)] (V5dipic-Cl), were synthesized with the indicated oxidation states. The present study was conducted to investigate if chemical valence and anti-oxidation effects of vanadium compounds are involved in the anti-diabetic effects observed in streptozotocin (STZ)-induced diabetic rats treated with these vanadium compounds. V3dipic-Cl, V4dipic-Cl, V5dipic-Cl, inorganic vanadium salts vanadyl sulfate (VOSO4) or sodium metavanadate (NaVO3) were orally administered in drinking water (50 μgV/ml) to STZ-induced diabetic rats for 28 days. The results showed that Vdipic-Cl treatment significantly improved hyperglycemia and glucose intolerance, as well as increased hepatic glycogen synthesis in diabetic rats. The mRNA levels of key glycolytic enzymes in liver, phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GK), and L-pyruvate kinase (L-PK) altered in diabetic animals were significantly restored towards normal values by treatment with some of the vanadium compounds. Moreover, the diabetes elevated activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in serum were significantly decreased after treatment with Vdipic-Cl complexes. Furthermore, treatment of diabetic rats with V4dipic-Cl and V5dipic-Cl compounds significantly reduced malondialdehyde (MDA) production and increased glutathione peroxidase (GSH-Px) and catalase (CAT) activities. These data suggest that vanadium compounds with the indicated chemical valence promote glycogen synthesis and recover suppressed glycolysis in the liver of diabetic rats due to their capacity to reduce oxidative stress by stimulating antioxidant enzymes.

摘要

钒化合物在体外和体内均发挥多种胰岛素模拟和抗糖尿病作用。合成了具有指定氧化态的钒（III、IV、V）-氯代二吡啶甲酸盐（Vdipic-Cl）化合物，包括H[V(III)(dipic-Cl)2]·5H2O（V3dipic-Cl）、V(IV)O(dipic-Cl)(H2O)2（V4dipic-Cl）和K[V(V)O2(dipic-Cl)]（V5dipic-Cl）。本研究旨在调查钒化合物的化学价和抗氧化作用是否与用这些钒化合物治疗的链脲佐菌素（STZ）诱导的糖尿病大鼠中观察到的抗糖尿病作用有关。将V3dipic-Cl、V4dipic-Cl、V5dipic-Cl、无机钒盐硫酸氧钒（VOSO4）或偏钒酸钠（NaVO3）以50μgV/ml的浓度加入饮用水中，口服给予STZ诱导的糖尿病大鼠，持续28天。结果表明，Vdipic-Cl治疗显著改善了糖尿病大鼠的高血糖和葡萄糖不耐受情况，并增加了肝糖原合成。糖尿病动物肝脏中关键糖酵解酶磷酸烯醇式丙酮酸羧激酶（PEPCK）、葡萄糖激酶（GK）和L-丙酮酸激酶（L-PK）的mRNA水平，经某些钒化合物治疗后显著恢复至正常值。此外，用Vdipic-Cl复合物治疗后，糖尿病导致的血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）活性升高显著降低。此外，用V4dipic-Cl和V5dipic-Cl化合物治疗糖尿病大鼠可显著降低丙二醛（MDA）的产生，并增加谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的活性。这些数据表明，具有指定化学价的钒化合物可促进糖尿病大鼠肝脏中的糖原合成并恢复受抑制的糖酵解，这是由于它们通过刺激抗氧化酶来降低氧化应激的能力。