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

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.

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Haase, H., Maret, W. Protein Tyrosine Phosphatases as Targets of the Combined Insulinomimetic Effects of Zinc and Oxidants. Biometals 18, 333–338 (2005). https://doi.org/10.1007/s10534-005-3707-9

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  • DOI: https://doi.org/10.1007/s10534-005-3707-9

Key words

  • diabetes
  • insulin signaling
  • PTP 1B
  • redox
  • zinc