Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
Department of Nursing, Meiho University, Pingtung, Taiwan.
Kaohsiung J Med Sci. 2018 Jan;34(1):14-21. doi: 10.1016/j.kjms.2017.08.009. Epub 2017 Sep 19.
Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance.
发芽糙米(PGBR)可改善代谢综合征,但目前有关 PGBR 提取物对胰岛素抵抗影响的研究并不多。本研究旨在探讨 PGBR 提取物对 TNF-α诱导的胰岛素抵抗的作用。将 HepG2 细胞(肝细胞)在 DMEM 培养基中培养,并加入 5μM 胰岛素或胰岛素和 30ng/ml TNF-α或胰岛素、TNF-α和 PGBR 提取物(50、100、300μg/ml)。培养基中的葡萄糖水平因胰岛素而降低,表明胰岛素促进葡萄糖进入细胞摄取。然而,TNF-α抑制了用胰岛素处理的细胞中葡萄糖的摄取。此外,胰岛素增加了 AMP 激活的蛋白激酶(AMPK)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇-3-激酶-α(PI3K-α)、丝氨酸/苏氨酸激酶 PI3K 连接蛋白激酶 B(Akt/PKB)、葡萄糖转运蛋白-2(GLUT-2)、葡萄糖激酶(GCK)、过氧化物酶体增殖物激活受体-α(PPAR-α)和 PPAR-γ 的蛋白表达。TNF-α 激活了 p65 和 MAPKs(JNK1/2 和 ERK1/2),这进一步恶化了 AMPK、IRS-1、PI3K-α、Akt/PKB、GLUT-2、GCK、糖原合酶激酶-3(GSK-3)、PPAR-α 和 PPAR-γ 的表达。一旦建立了这种关系,我们就将 PGBR 提取物添加到含有胰岛素和 TNF-α的细胞中。我们发现培养基中的葡萄糖水平降低,并且 AMPK、IRS-1、PI3K-α、Akt/PKB、GLUT-2、GCK、GSK-3、PPAR-α、PPAR-γ 和 p65、JNK1/2 的蛋白表达也得到恢复。总之,本研究发现 TNF-α 抑制了胰岛素刺激的葡萄糖摄取,并加重了相关蛋白的表达,表明其可能导致胰岛素抵抗。PGBR 提取物可改善 TNF-α 诱导的胰岛素抵抗,表明其将来可能用于帮助控制胰岛素抵抗。