期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 305, 期 11, 页码 E1408-E1414出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00212.2013
关键词
skeletal muscle; sestrin 3; type 2 diabetes
资金
- Karolinska Institutet, European Research Council Ideas Program (ICEBERG) [ERC-2008-AdG23285]
- Swedish Research Council
- Swedish Diabetes Association
- Strategic Research Foundation
- Knut and Alice Wallenberg Foundation
- Stockholm County Council
In mammals, the sestrin family is composed of three stress-responsive genes. Ablation of sestrin in Drosophila attenuates longevity, which is accompanied by increased S6K phosphorylation and decreased AMPK phosphorylation. Nevertheless, the metabolic role of sestrins in mammals is not comprehensively understood. We characterized the expression of individual sestrin family members and determined their role in vastus lateralis muscle biopsies from participants with normal glucose tolerance (NGT) or type 2 diabetes (T2D). Expression of sestrin 1 or sestrin 2 mRNA was unaltered between the NGT and T2D participants. Conversely, sestrin 3 mRNA was increased in T2D patients and correlated with fasting plasma glucose, 2-h postprandial plasma glucose and HbA(1c). A trend for increased sestrin 3 protein was observed in T2D patients. In human primary myotubes, sestrin 3 mRNA increased during differentiation, and this response was unaltered in T2D-derived myotubes. Long-term treatment of myotubes with insulin or AICAR decreased sestrin 3 mRNA. Exposure of myotubes to the reactive oxygen species H2O2 increased mRNA expression of sestrin 1 and 2, whereas sestrin 3 was unaltered. siRNA-mediated silencing of sestrin 3 in myotubes was without effect on insulin-stimulated glucose incorporation into glycogen or AICAR-stimulated palmitate oxidation. These results provide evidence against sestrin 3 in the direct control of glucose or lipid metabolism in human skeletal muscle. However, siRNA-mediated sestrin 3 gene silencing in myotubes increased myostatin expression. Collectively, our results indicate sestrin 3 is upregulated in T2D and could influence skeletal muscle differentiation without altering glucose and lipid metabolism.
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