Impact of Divergent Effects of Astaxanthin on Insulin Signaling in L6 Cells
Impact of Divergent Effects of Astaxanthin on Insulin Signaling in L6 Cells
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DOI：
10.1210/en.2012-2198
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发表时间：
2013-08-01
期刊：
影响因子：
4.8
通讯作者：
Tobe, Kazuyuki
中科院分区：
文献类型：
--
作者：
Ishiki, Manabu;Nishida, Yasuhiro;Tobe, Kazuyuki
由于氧化应激促进肥胖和2型糖尿病的胰岛素抵抗，因此找到有效的抗氧化剂以降低这种威胁至关重要。在这项研究中，我们探讨了虾青素，类胡萝卜素抗氧化剂，对胰岛素信号转导的影响，并调查是否虾青素改善细胞因子和游离脂肪酸诱导的胰岛素抵抗体外。我们研究了虾青素对胰岛素刺激的葡萄糖转运蛋白4（GLUT 4）易位，葡萄糖摄取，和胰岛素信号在培养的大鼠L 6肌细胞使用质膜草坪试验，2-脱氧葡萄糖摄取，和蛋白质印迹分析的影响。接下来，我们研究了虾青素对TNF α和棕榈酸诱导的胰岛素抵抗的影响。通过二氯荧光素染色评估由TNF α或棕榈酸酯与或不与虾青素产生的活性氧物质的量。我们还比较了虾青素对胰岛素信号传导的影响与其他抗氧化剂，α-硫辛酸和α-生育酚。我们观察到虾青素增强胰岛素刺激的GLUT 4易位和葡萄糖摄取，这与胰岛素受体底物-1酪氨酸和Akt磷酸化的增加以及c-Jun N-末端激酶（JNK）和胰岛素受体底物-1丝氨酸307磷酸化的减少有关。此外，虾青素恢复了TNF α和棕榈酸诱导的胰岛素刺激的GLUT 4易位或葡萄糖摄取的减少，同时减少了活性氧的产生。α-硫辛酸增强Akt磷酸化，降低ERK和JNK磷酸化，而α-生育酚增强ERK和JNK磷酸化，但对Akt磷酸化几乎没有影响。总的来说，这些发现表明，虾青素是一种非常有效的抗氧化剂，通过保护细胞免受由各种刺激物（包括TNF α和棕榈酸酯）产生的氧化应激而改善胰岛素抵抗。
Because oxidative stress promotes insulin resistance in obesity and type 2 diabetes, it is crucial to find effective antioxidant for the purpose of decreasing this threat. In this study, we explored the effect of astaxanthin, a carotenoid antioxidant, on insulin signaling and investigated whether astaxanthin improves cytokine- and free fatty acid-induced insulin resistance in vitro. We examined the effect of astaxanthin on insulin-stimulated glucose transporter 4 (GLUT4) translocation, glucose uptake, and insulin signaling in cultured rat L6 muscle cells using plasma membrane lawn assay, 2-deoxyglucose uptake, and Western blot analysis. Next, we examined the effect of astaxanthin on TNF alpha- and palmitate-induced insulin resistance. The amount of reactive oxygen species generated by TNF alpha or palmitate with or without astaxanthin was evaluated by dichlorofluorescein staining. We also compared the effect of astaxanthin on insulin signaling with that of other antioxidants, alpha-lipoic acid and alpha-tocopherol. We observed astaxanthin enhanced insulin-stimulated GLUT4 translocation and glucose uptake, which was associated with an increase in insulin receptor substrate-1 tyrosine and Akt phosphorylation and a decrease in c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 serine 307 phosphorylation. Furthermore, astaxanthin restored TNF alpha- and palmitate-induced decreases in insulin-stimulated GLUT4 translocation or glucose uptake with a concomitant decrease in reactive oxygen species generation. alpha-Lipoic acid enhanced Akt phosphorylation and decreased ERK and JNK phosphorylation, whereas alpha-tocopherol enhanced ERK and JNK phosphorylation but had little effect on Akt phosphorylation. Collectively these findings indicate astaxanthin is a very effective antioxidant for ameliorating insulin resistance by protecting cells from oxidative stress generated by various stimuli including TNF alpha and palmitate.