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): 14608-13, 2011 Aug 30.
Article
in En
| MEDLINE
| ID: mdl-21873205
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Signal Transduction
/
Reactive Oxygen Species
/
Muscle, Skeletal
/
Sirtuin 3
/
Mitochondria
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2011
Document type:
Article
Affiliation country:
United States