Journal
BIOMETALS
Volume 18, Issue 4, Pages 333-338Publisher
SPRINGER
DOI: 10.1007/s10534-005-3707-9
Keywords
diabetes; insulin signaling; PTP 1B; redox; zinc
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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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