Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity

DOI Web Site 被引用文献24件
  • Dudley W. Lamming
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Lan Ye
    Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Pekka Katajisto
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Marcus D. Goncalves
    Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Maki Saitoh
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Deanna M. Stevens
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • James G. Davis
    Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Adam B. Salmon
    The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
  • Arlan Richardson
    The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
  • Rexford S. Ahima
    Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • David A. Guertin
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • David M. Sabatini
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Joseph A. Baur
    Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

説明

<jats:title>Dissecting Rapamycin Responses</jats:title> <jats:p> Long-term treatment of mice and other organisms with the drug rapamycin extends life span. But, at the same time, the drug disrupts metabolic regulation and the action of the hormone insulin. <jats:bold> Lamming <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1638" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1215135">1638</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6076" page="1578" related-article-type="in-this-issue" vol="335" xlink:href="10.1126/science.1221365">Hughes and Kennedy</jats:related-article> </jats:bold> ) dissected the action of rapamycin in genetically modified mice and found, encouragingly, that these two actions of rapamycin can be separated. Rapamycin inhibits a protein kinase complex known as mTORC1, and this appears to provide most of the life-lengthening effects of the drug. However, rapamycin also acts on a related complex known as mTORC2, and it is the disruption of mTORC2 action that produces the diabetic-like symptoms of decreased glucose tolerance and insensitivity to insulin. </jats:p>

収録刊行物

  • Science

    Science 335 (6076), 1638-1643, 2012-03-30

    American Association for the Advancement of Science (AAAS)

被引用文献 (24)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ