Protein Tyrosine Phosphatases as Targets of the Combined Insulinomimetic Effects of Zinc and Oxidants
- 1 August 2005
- journal article
- review article
- Published by Springer Science and Business Media LLC in BioMetals
- Vol. 18 (4), 333-338
- https://doi.org/10.1007/s10534-005-3707-9
Abstract
Zinc ions have an insulin-like (insulinomimetic) effect. A particularly sensitive target of zinc ions is protein tyrosine phosphatase 1B (PTP 1B), a key regulator of the phosphorylation state of the insulin receptor. Modulation of insulin signaling by zinc chelating agents and the recognition of temporal and spatial fluctuations of zinc suggest a physiological role of zinc in insulin signal transduction. Tyrosine phosphatases seem to be regulated jointly by insulin-induced redox (hydrogen peroxide) signaling, which results in their oxidative inactivation, and by their zinc inhibition after oxidative zinc release from other proteins. In␣diabetes, the significant oxidative stress and associated changes in zinc metabolism modify the cell’s response and sensitivity to insulin. Zinc deficiency activates stress pathways and may result in a loss of tyrosine phosphatase control, thereby causing insulin resistance.Keywords
This publication has 56 references indexed in Scilit:
- Protein Tyrosine Phosphatases in the Human GenomeCell, 2004
- Chromium and insulin resistanceNutrition Research Reviews, 2003
- Coordinated action of protein tyrosine phosphatases in insulin signal transductionEuropean Journal of Biochemistry, 2002
- Catalytic selenols couple the redox cycles of metallothionein and glutathioneEuropean Journal of Biochemistry, 2001
- Functions of zinc in signaling, proliferation and differentiation of mammalian cellsBioMetals, 2001
- Zinc, Insulin and DiabetesJournal of the American College of Nutrition, 1998
- Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) miceBiological Trace Element Research, 1998
- Obesity and hyperleptinemia in metallothionein (-I and -II) null miceProceedings of the National Academy of Sciences, 1998
- Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transductionMolecular and Cellular Biochemistry, 1998
- Protein-Tyrosine Phosphatase 1B Complexes with the Insulin Receptor in Vivo and Is Tyrosine-phosphorylated in the Presence of InsulinJournal of Biological Chemistry, 1997