Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants

Biometals. 2005 Aug;18(4):333-8. doi: 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromium / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Insulin / metabolism*
  • Insulin Resistance
  • Models, Biological
  • Oxidants / pharmacology*
  • Oxidation-Reduction
  • Oxygen / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism
  • Protein Tyrosine Phosphatases / physiology*
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Zinc / chemistry
  • Zinc / pharmacology*
  • Zinc Compounds / pharmacology

Substances

  • Insulin
  • Oxidants
  • Zinc Compounds
  • Chromium
  • Hydrogen Peroxide
  • Receptor, Insulin
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Zinc
  • Oxygen