Scholars@Duke publication: Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production.

Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production.

Publication , Journal Article

Jing, E; Emanuelli, B; Hirschey, MD; Boucher, J; Lee, KY; Lombard, D; Verdin, EM; Kahn, CR

Published in: Proc Natl Acad Sci U S A

August 30, 2011

Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle.

Duke Scholars

Author Matthew Hirschey Medicine, Endocrinology, Metabolism, and Nutrition

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Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.1111308108

EISSN

1091-6490

Publication Date

August 30, 2011

Volume

108

Issue

Start / End Page

14608 / 14613

Location

United States

Related Subject Headings

Sirtuin 3
Signal Transduction
Reactive Oxygen Species
Phosphorylation
Oxidation-Reduction
Myoblasts
Muscle, Skeletal
Mitochondria
Mice, Knockout
Mice, Inbred C57BL

Citation

APA

Chicago

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MLA

NLM

Jing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., … Kahn, C. R. (2011). Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A, 108(35), 14608–14613. https://doi.org/10.1073/pnas.1111308108

Jing, Enxuan, Brice Emanuelli, Matthew D. Hirschey, Jeremie Boucher, Kevin Y. Lee, David Lombard, Eric M. Verdin, and C Ronald Kahn. “Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production.” Proc Natl Acad Sci U S A 108, no. 35 (August 30, 2011): 14608–13. https://doi.org/10.1073/pnas.1111308108.

Jing E, Emanuelli B, Hirschey MD, Boucher J, Lee KY, Lombard D, et al. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14608–13.

Jing, Enxuan, et al. “Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production.” Proc Natl Acad Sci U S A, vol. 108, no. 35, Aug. 2011, pp. 14608–13. Pubmed, doi:10.1073/pnas.1111308108.

Jing E, Emanuelli B, Hirschey MD, Boucher J, Lee KY, Lombard D, Verdin EM, Kahn CR. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14608–14613.