Affordable Access

deepdyve-link
Publisher Website

Molecular mechanism of antidiabetic zinc-allixin complexes: regulations of glucose utilization and lipid metabolism.

Authors
  • Nakayama, Akihiro1
  • Hiromura, Makoto
  • Adachi, Yusuke
  • Sakurai, Hiromu
  • 1 Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan. , (Japan)
Type
Published Article
Journal
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
Publication Date
Jun 01, 2008
Volume
13
Issue
5
Pages
675–684
Identifiers
DOI: 10.1007/s00775-008-0352-0
PMID: 18288506
Source
Medline
License
Unknown

Abstract

We previously reported new zinc complexes of allixin [bis(allixinato)zinc] and its derivative bis(thioallixin-N-methyl)zinc that demonstrated excellent antidiabetic activity in type 2 diabetic mellitus KKA(y) mice. However, the molecular mechanism of these complexes is not fully understood. Thus, we attempted to reveal the intracellular mechanism of these complexes in 3T3-L1 adipocytes. Both zinc complexes induced Akt/protein kinase B (Akt/PKB) phosphorylation. The phosphorylation of Akt/PKB enhanced glucose transporter 4 translocation to the plasma membrane; this in turn enhanced the glucose utilization in a dose- and time-dependent manner. Glucose utilization by the complexes depended on the intracellular zinc concentration. Moreover, zinc complexes suppressed the cyclic AMP dependent protein kinase mediated phosphorylation of hormone-sensitive lipase (HSL), leading to the inhibition of free fatty acid release from the 3T3-L1 adipocytes. Such responses were inhibited by wortmannin, suggesting that the suppression of HSL by zinc complexes was dependent in the phosphoinositide 3-kinase-Akt/PKB signaling cascade. On the basis of these results, we proposed that both zinc complexes activated the Akt/PKB-mediated insulin-signaling pathway and improved both glucose utilization and lipid metabolism.

Report this publication

Statistics

Seen <100 times