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 language | English |
|---|---|
| Pages (from-to) | 102-106 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 295 |
| Issue number | 1 |
| DOIs | |
| State | Published - 5 Jul 2002 |
| Externally published | Yes |
Bibliographical note
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.
Funding
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.
| Funders | Funder number |
|---|---|
| Israel Diabetes Foundation |
Keywords
- Glycogen synthase kinase-3
- Insulin signaling
- Zinc ions
