Inhibition of glycogen synthase kinase-3β by bivalent zinc ions: Insight into the insulin-mimetic action of zinc

Ronit Ilouz, Oksana Kaidanovich, David Gurwitz, Hagit Eldar-Finkelman

Research output: Contribution to journalArticlepeer-review

Abstract

Zinc is an important trace element found in most body tissues as bivalent cations and has essential roles in human health. The insulin-like effect of zinc cations raises the possibility that they inhibit glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase linked with insulin resistance and type 2 diabetes. Here we show that physiological concentrations of zinc ions directly inhibit GSK-3β in vitro in an uncompetitive manner. Treatment of HEK-293 cells with zinc enhanced glycogen synthase activity and increased the intracellular levels of β-catenin, providing evidence for inhibition of endogenous GSK-3β by zinc. Moreover, zinc ions enhanced glucose uptake 3-fold in isolated mouse adipocytes, an increase similar to activation with saturated concentrations of insulin. We propose that the in vivo insulin-mimetic actions of zinc are mediated via direct inhibition of endogenous GSK-3β.

Original languageEnglish
Pages (from-to)102-106
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume295
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Glycogen synthase kinase-3
  • Insulin signaling
  • Zinc ions

Fingerprint

Dive into the research topics of 'Inhibition of glycogen synthase kinase-3β by bivalent zinc ions: Insight into the insulin-mimetic action of zinc'. Together they form a unique fingerprint.

Cite this