TY - JOUR
T1 - Inhibition of glycogen synthase kinase-3β by bivalent zinc ions
T2 - Insight into the insulin-mimetic action of zinc
AU - Ilouz, Ronit
AU - Kaidanovich, Oksana
AU - Gurwitz, David
AU - Eldar-Finkelman, Hagit
N1 - Funding 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.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Glycogen synthase kinase-3
KW - Insulin signaling
KW - Zinc ions
UR - http://www.scopus.com/inward/record.url?scp=0036302005&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(02)00636-8
DO - 10.1016/S0006-291X(02)00636-8
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AN - SCOPUS:0036302005
SN - 0006-291X
VL - 295
SP - 102
EP - 106
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
