期刊
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
卷 48, 期 5, 页码 440-446出版社
ASSOC BRAS DIVULG CIENTIFICA
DOI: 10.1590/1414-431X20144238
关键词
Silibinin; Insulin resistance; Palmitate; C2C12
资金
- Doctoral Fund of the Ministry of Education of China [20093317120003]
- Key Program of School Foundation of Zhejiang University of Technology [2012XZ004]
- Natural Science Foundation of Zhejiang Province [Y14H310011]
- Chinese Key Laboratory for Biomedical Engineering of the Ministry of Education
The present study investigated the effect of silibinin, the principal potential anti-inflammatory flavonoid contained in silymarin, a mixture of flavonolignans extracted from Silybum marianum seeds, on palmitate-induced insulin resistance in C2C12 myotubes and its potential molecular mechanisms. Silibinin prevented the decrease of insulin-stimulated 2-NBDG (2-[N-(7-nitrobenz-2-oxa- 1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) uptake and the downregulation of glutamate transporter type 4 (GLUT4) translocation in C2C12 myotubes induced by palmitate. Meanwhile, silibinin suppressed the palmitate-induced decrease of insulin-stimulated Akt Ser473 phosphorylation, which was reversed by wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K). We also found that palmitate downregulated insulin-stimulated Tyr632 phosphorylation of insulin receptor substrate 1 (IRS-1) and up-regulated IRS-1 Ser307 phosphorylation. These effects were rebalanced by silibinin. Considering several serine/threonine kinases reported to phosphorylate IRS-1 at Ser307, treatment with silibinin downregulated the phosphorylation of both c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B kinase beta (IKK beta), which was increased by palmitate in C2C12 myotubes mediating inflammatory status, whereas the phosphorylation of PKC-h was not significantly modulated by silibinin. Collectively, the results indicated that silibinin prevented inhibition of the IRS-1/PI3K/Akt pathway, thus ameliorating palmitate-induced insulin resistance in C2C12 myotubes.
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