Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition.
Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition.
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DOI：
10.1590/1414-431x20144238
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Jiang WJ
中科院分区：
文献类型：
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作者：
Li HB;Yang YR;Mo ZJ;Ding Y;Jiang WJ
本研究探讨了水飞蓟素中主要的潜在抗炎黄酮类化合物水飞蓟宾对棕榈酸诱导的C2 C12肌管胰岛素抵抗的影响及其潜在的分子机制。水飞蓟宾可阻止棕榈酸诱导的胰岛素刺激的C2 C12肌管2-NBDG（2-[N-（7-nitrobenz-2-oxa-1，3-diazol-4-yl）amino]-2-deoxy-D-glucose）摄取的减少和谷氨酸转运体4型（GLUT 4）转位的下调。同时，水飞蓟宾抑制棕榈酸诱导的胰岛素刺激的Akt Ser 473磷酸化的减少，这是逆转磷脂酰肌醇-3-激酶（PI 3 K）的特异性抑制剂渥曼青霉素。我们还发现，棕榈酸下调胰岛素刺激的胰岛素受体底物1（IRS-1）的Tyr 632磷酸化和上调IRS-1 Ser 307磷酸化。这些作用被水飞蓟宾重新平衡。考虑到报道的几种丝氨酸/苏氨酸激酶在Ser 307磷酸化IRS-1，水飞蓟宾治疗下调c-Jun N-末端激酶（JNK）和核因子-κB激酶β（IKKβ）的磷酸化，其在介导炎症状态的C2 C12肌管中被棕榈酸盐增加，而PKC-θ的磷酸化不受水飞蓟宾显著调节。总的来说，结果表明，水飞蓟宾阻止IRS-1/PI 3 K/Akt通路的抑制，从而改善棕榈酸诱导的C2 C12肌管胰岛素抵抗。
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-κB kinase β (IKKβ), which was increased by palmitate in C2C12 myotubes mediating inflammatory status, whereas the phosphorylation of PKC-θ 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.