Insulinomimetic Zn complex (Zn(opt)2) enhances insulin signaling pathway in 3T3-L1 adipocytes
Insulinomimetic Zn complex (Zn(opt)2) enhances insulin signaling pathway in 3T3-L1 adipocytes
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DOI：
10.1016/j.jinorgbio.2006.12.015
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发表时间：
2007-04-01
影响因子：
3.9
通讯作者：
Sakurai, Hiromu
中科院分区：
文献类型：
--
作者：
Basuki, Wanny;Hiromura, Makoto;Sakurai, Hiromu
锌是一种必需的微量元素，具有多种调节功能，参与胰岛素的合成、分泌、信号转导和葡萄糖转运。自2000年以来，我们提出了不同配位环境的锌配合物在2型糖尿病动物体内表现出较高的拟胰岛素活性和抗糖尿病活性。然而，其活性的分子机制仍未解决。本研究旨在从胰岛素信号转导途径的角度揭示3T3-L1脂肪细胞中几种锌络合物的分子机制。结果表明，在S_2O_2配位环境下，双(1-氧基-2-吡啶-硫代)锌(II)、锌(OPT)(2)对Akt/蛋白激酶B(Akt/PKB)的磷酸化诱导作用最强，在25mU M时磷酸化效果最好，而100 nM的Wortmannin抑制了这种由双(1-氧-2-吡啶-硫代)锌(2)诱导的Akt/PKB磷酸化。此外，磷酸化在刺激5~10min时达到最大，与锌的摄取一致，在刺激5~10min时也达到最大。Akt/PKB的磷酸化具有浓度和时间依赖性。锌(Opt)(2)还能将GLUT4蛋白转移到质膜上。我们的结论是，锌(Opt)(2)通过Akt/PKB的磷酸化激活胰岛素信号通路，进而导致GLUT4从胞浆到质膜的移位，从而显示出胰岛素仿生和抗糖尿病活性。(C)2007 Elsevier Inc.保留所有权利。
Zinc (Zn) is an essential trace element with multiple regulatory functions, involving insulin synthesis, secretion, signaling and glucose transport. Since 2000, we have proposed that Zn complexes with different coordination environments exhibit high insulmomimetic and antidiabetic activities in type 2 diabetic animals. However, the molecular mechanism for the activities is still unsolved. The purpose of this study was to reveal the molecular mechanism of several types of Zn complexes in 3T3-L1 adipocytes, with respect to insulin signaling pathway. Obtained results shows that bis(1-oxy-2-pyridine-thiolato)Zn(II), Zn(opt)(2), with S2O2 coordination environment induced most strongly Akt/protein kinase B (Akt/PKB) phosphorylation, in which the optimal phosphorylation was achieved at a concentration of 25 mu M, and this Zn(opt)(2)-induced Akt/PKB phosphorylation was inhibited by wortmannin at 100 nM. Further, the phosphorylation was maximal at 5-10 min stimulation, in agreement with the Zn uptake which was also maximal at 5-10 min stimulation. The Akt/ PKB phosphorylation was in concentration- and time-dependent manners. Zn(opt)(2) was also capable to translocate GLUT4 protein to the plasma membrane. We conclude that Zn(opt)(2) was revealed to exhibit both insulinomimetic and antidiabetic activities by activating insulin signaling cascade through Akt/PKB phosphorylation, which in turn caused the GLUT4 translocation from the cytosol to the plasma membrane. (c) 2007 Elsevier Inc. All rights reserved.