Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity-Reference-Cited by-同舟云学术

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

Published:2012-03-30 Issue:6076 Volume:335 Page:1638-1643
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lamming Dudley W.¹²³⁴⁵,Ye Lan⁶,Katajisto Pekka¹²³⁴⁵,Goncalves Marcus D.⁷,Saitoh Maki¹²³⁴⁵,Stevens Deanna M.¹²³⁴⁵,Davis James G.⁶,Salmon Adam B.⁸,Richardson Arlan⁸,Ahima Rexford S.⁷,Guertin David A.¹²³⁴⁵,Sabatini David M.¹²³⁴⁵,Baur Joseph A.⁶

Affiliation:

1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

2. Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

3. Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA.

4. Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, MA 02142, USA.

5. The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.

6. Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

7. Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

8. The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.

Abstract

Dissecting Rapamycin Responses 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. Lamming et al. (p. 1638 ; see the Perspective by

Hughes and Kennedy

) 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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