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

Biochem Biophys Res Commun. 2002 Jul 5;295(1):102-6. doi: 10.1016/s0006-291x(02)00636-8.


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-3beta (GSK-3beta), 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-3beta in vitro in an uncompetitive manner. Treatment of HEK-293 cells with zinc enhanced glycogen synthase activity and increased the intracellular levels of beta-catenin, providing evidence for inhibition of endogenous GSK-3beta 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-3beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Biological Transport / drug effects
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Line
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Glucose / metabolism
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Insulin / pharmacology
  • Mice
  • Zinc / pharmacology*


  • Enzyme Inhibitors
  • Insulin
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3
  • Glucose
  • Zinc