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.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 2002|
Bibliographical noteFunding Information:
This work was supported by the Israel Diabetes Foundation (ISDF) and the Annual Award of the Hendrik and Irene Gutwirth Research Prize in Diabetes Mellitus awarded to H. Eldar-Finkelman.
- Glycogen synthase kinase-3
- Insulin signaling
- Zinc ions