Suppression of Free Fatty Acid-Induced Insulin Resistance by Phytopolyphenols in C2C12 Mouse Skeletal Muscle Cells
Suppression of Free Fatty Acid-Induced Insulin Resistance by Phytopolyphenols in C2C12 Mouse Skeletal Muscle Cells
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DOI：
10.1021/jf204496f
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发表时间：
2012-02-01
影响因子：
6.1
通讯作者：
Lin, Jen-Kun
中科院分区：
文献类型：
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作者：
Deng, Yea-Tzy;Chang, Tsai-Wen;Lin, Jen-Kun
据报道，血浆游离脂肪酸(FFAs)水平升高与骨骼肌胰岛素抵抗密切相关，也可能在肥胖和2型糖尿病的胰岛素抵抗中起关键作用。骨骼肌是胰岛素刺激葡萄糖摄取的主要部位，参与能量调节和动态平衡。在这项研究中，我们使用了蛋白激酶C(PKC)激活剂12-O-十四酰佛波醇13-乙酸酯(TPA)和棕榈酸酯来诱导C2C12小鼠骨骼肌细胞的胰岛素抵抗。我们的数据显示，表没食子儿茶素没食子酸酯(EGCG)和姜黄素处理降低了胰岛素受体底物-1(IRS-1)Ser307的磷酸化，而姜黄素更有效地增加了TPA诱导的Akt的磷酸化。此外，表儿茶素没食子酸酯可抑制IRS-1 Ser307的磷酸化，显著促进Akt、ERK1/2、p38MAPK和AMP激活的蛋白激酶的活化。随着棕榈酸酯作用时间的延长，IRS-1的表达显著降低，EGCG、心电和姜黄素可逆转C2C12骨骼肌细胞IRS-1的表达、Akt磷酸化和MAPK信号通路的激活，并改善葡萄糖摄取，尤其是心电和姜黄素。此外，用这些多酚处理可以抑制乙酰辅酶A羧基酶的激活，但只有EGCG才能抑制细胞内的脂质积累。这些结果可能提示姜黄素改善FFA诱导的胰岛素抵抗的能力比其他两种药物更好，而心电图在减轻胰岛素抵抗方面比EGCG更有效。
It was reported that increased plasma levels of free fatty acids (FFAs) are associated with profound insulin resistance in skeletal muscle and may also play a critical role in the insulin resistance of obesity and type 2 diabetes mellitus. Skeletal muscle is the major site for insulin-stimulated glucose uptake and is involved in energy regulation and homeostasis. In this study, we used 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC) activator, and palmitate to induce insulin resistance in C2C12 mouse skeletal muscle cells. Our data show that epigallocatechin gallate (EGCG) and curcumin treatment reduce insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, and curcumin is more potent to increase Akt phosphorylation in TPA induction. Moreover, we found that after 5 h of palmitate incubation, epicatechin gallate (ECG) can suppress IRS-1 Ser307 phosphorylation and significantly promote Akt, ERK1/2, p38 MAPK, and AMP-activated protein kinase activation. With a longer incubation with palmitate, IRS-1 exhibited a dramatic depletion, and treatment with EGCG, ECG, and curcumin could reverse IRS-1 expression, Akt phosphorylation, and MAPK signaling cascade activation and improve glucose uptake in C2C12 skeletal muscle cells, especially ECG and curcumin. In addition, treatment with these polyphenols can suppress acetyl-CoA carboxylase activation, but only EGCG could inhibit lipid accumulation in the intracellular site. These findings may suggest that curcumin shows the best capacity to improve FFA-induced insulin resistance than the other two, and ECG was more effective than EGCG in attenuating insulin resistance.