Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor γ and fatty acid transferase expressions
Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor γ and fatty acid transferase expressions
复制标题
小檗碱通过抑制过氧化物酶体增殖物激活受体 γ 和脂肪酸转移酶的表达，改善 L6 肌管中游离脂肪酸诱导的胰岛素抵抗。
DOI：
10.1016/j.metabol.2009.06.009
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发表时间：
2009-12-01
影响因子：
9.8
通讯作者：
Sun, Changhao
中科院分区：
文献类型：
--
作者：
Chen, Yanfeng;Li, Ying;Sun, Changhao
植物生物碱小檗碱（BBR）已被报道在人类和动物中具有抗糖尿病作用。然而，其作用机制尚不清楚。本研究旨在探讨BBR对游离脂肪酸（FFA）诱导的肌细胞胰岛素抵抗的影响及其作用机制。通过用250 μ mol/L棕榈酸处理L 6肌管，在L 6肌管中建立FFA诱导的胰岛素抵抗细胞模型。在培养基中加入FFA使过氧化物酶体增殖物激活受体γ（PPAR γ）和脂肪酸转移酶（FAT/CD 36）的表达分别增加了26%和50%，葡萄糖消耗量减少了43%，胰岛素介导的葡萄糖摄取量减少了63%。小檗碱处理增加正常细胞的葡萄糖消耗和胰岛素刺激的葡萄糖摄取，并改善FFA诱导的胰岛素抵抗细胞的葡萄糖摄取。BBR对葡萄糖摄取的改善伴随着PPAR γ和FAT/CD 36蛋白表达的剂量依赖性降低。在胰岛素抵抗的肌管中，BBR（5 μ mol/L）使PPAR γ和FAT/CD 36蛋白降低31%和24%，而PPAR γ拮抗剂GW 9662使这两种蛋白分别降低56%和46%。相比之下，PPAR γ激动剂罗格列酮分别使PPAR γ和FAT/CD 36的表达增加34%和21%。我们的研究结果表明，BBR改善FFA诱导的胰岛素抵抗的肌管通过抑制脂肪酸摄取至少部分通过减少过氧化物酶体增殖物激活受体γ和FAT/CD 36的表达。(C)2009年由Elsevier Inc.出版
The plant alkaloid berberine (BBR) has been reported to have antidiabetic effect in humans and animals. However, the mechanism of action is not well understood. The present study was conducted to determine the effect and mechanism of action of BBR on the free-fatty-acid (FFA)-induced insulin resistance in muscle cells. The FFA-induced insulin-resistant cell model was established in L6 myotubes by treating them with 250 mu mol/L of palmitic acid. The inclusion of FFA in the medium increased peroxisome proliferator-activated receptor gamma (PPAR gamma) and fatty acid transferase (FAT/CD36) expressions by 26% and 50% and decreased glucose consumption by 43% and insulin-mediated glucose uptake by 63%, respectively. Berberine treatment increased the glucose consumption and insulin-stimulated glucose uptake in normal cells and improved glucose uptake in the FFA-induced insulin-resistant cells. The improved glucose uptake by BBR was accompanied with a dose-dependent decrease in PPAR gamma and FAT/CD36 protein expressions. In insulin-resistant myotubes, BBR (5 mu mol/L) decreased PPAR gamma and FAT/CD36 proteins by 31% and 24%, whereas PPAR gamma antagonist GW9662 reduced both proteins by 56% and 46%, respectively. In contrast, PPAR gamma agonist rosiglitazone increased the expression of PPAR gamma and FAT/CD36 by 34% and 21%, respectively. Our results suggest that BBR improves the FFA-induced insulin resistance in myotubes through inhibiting fatty acid uptake at least in part by reducing PPAR gamma and FAT/CD36 expressions. (C) 2009 Published by Elsevier Inc.