Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 101, Issue 4, Pages 692-699Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2006.12.015
Keywords
insulinomimetic; Zn complex; Akt/PKB phosphorylation; GLUT4 translocation; 3T3-L1 adipocytes
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available