Insulin induces calcium signals in the nucleus of rat hepatocytes

Authors

  • Michele A. Rodrigues,

    1. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
    2. Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Dawidson A. Gomes,

    1. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
    2. Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Viviane A. Andrade,

    1. Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • M. Fatima Leite,

    1. Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Michael H. Nathanson

    Corresponding author
    1. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
    • Digestive Diseases Section, Room TAC S241D, Yale University School of Medicine, New Haven, CT 06520-8019
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    • fax: 203-785-4306.


  • Potential conflict of interest: Nothing to report.

Abstract

Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration. (HEPATOLOGY 2008.)

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