, Volume 18, Issue 4, pp 333–338 | Cite as

Protein Tyrosine Phosphatases as Targets of the Combined Insulinomimetic Effects of Zinc and Oxidants

  • Hajo Haase
  • Wolfgang Maret


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.

Key words

diabetes insulin signaling PTP 1B redox zinc 


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Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Institute of ImmunologyUniversity Hospital RWTH AachenGermany
  2. 2.Departments of Preventive Medicine & Community Health and AnesthesiologyUniversity of Texas Medical BranchGalvestonUSA

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