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Cellular chromium enhances activation of insulin receptor kinase.

Abstract

Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes.

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  • Authors+Show Affiliations

    ,

    Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908-0577, USA.

    ,

    Source

    Biochemistry 44:22 2005 Jun 07 pg 8167-75

    MeSH

    Amino Acid Sequence
    Animals
    CHO Cells
    Cell Membrane
    Chromium
    Cricetinae
    Enzyme Activation
    Enzyme Inhibitors
    Glutathione Transferase
    Humans
    Insulin
    Molecular Sequence Data
    Oxidation-Reduction
    Phosphorylation
    Protein Structure, Tertiary
    Protein Tyrosine Phosphatase, Non-Receptor Type 1
    Protein Tyrosine Phosphatases
    Receptor, Insulin
    Recombinant Fusion Proteins
    Tyrosine

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15924436

    Citation

    Wang, Hong, et al. "Cellular Chromium Enhances Activation of Insulin Receptor Kinase." Biochemistry, vol. 44, no. 22, 2005, pp. 8167-75.
    Wang H, Kruszewski A, Brautigan DL. Cellular chromium enhances activation of insulin receptor kinase. Biochemistry. 2005;44(22):8167-75.
    Wang, H., Kruszewski, A., & Brautigan, D. L. (2005). Cellular chromium enhances activation of insulin receptor kinase. Biochemistry, 44(22), pp. 8167-75.
    Wang H, Kruszewski A, Brautigan DL. Cellular Chromium Enhances Activation of Insulin Receptor Kinase. Biochemistry. 2005 Jun 7;44(22):8167-75. PubMed PMID: 15924436.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cellular chromium enhances activation of insulin receptor kinase. AU - Wang,Hong, AU - Kruszewski,Allison, AU - Brautigan,David L, PY - 2005/6/1/pubmed PY - 2005/8/27/medline PY - 2005/6/1/entrez SP - 8167 EP - 75 JF - Biochemistry JO - Biochemistry VL - 44 IS - 22 N2 - Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/15924436/full_citation L2 - https://dx.doi.org/10.1021/bi0473152 DB - PRIME DP - Unbound Medicine ER -