Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2 liver cells
Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2 liver cells
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DOI：
10.3109/08923970903252220
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Chae, Han-Jung
中科院分区：
文献类型：
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作者：
Kim, Do-Sung;Jeong, Seul-Ki;Chae, Han-Jung
肝脏过度供应脂肪酸会导致肝脏胰岛素抵抗和与肥胖或 2 型糖尿病相关的内质网 (ER) 应激。此外，过度和/或长期的内质网应激会导致肝细胞死亡，从而使非酒精性脂肪肝病恶化为脂肪性肝炎。本研究的目的是研究二甲双胍对棕榈酸酯诱导的 HepG2 细胞内质网应激和肝胰岛素抵抗的影响。二甲双胍通过 caspase-3 激活显着抑制棕榈酸酯诱导的细胞死亡和凋亡。二甲双胍还阻断 ER 应激蛋白（GRP78、Chop、Cleaved ATF-6、p-eIF2 α 和 XBP-1）的诱导，并调节 IRS-1 的丝氨酸磷酸化。因此，二甲双胍可以保护肝细胞免受饱和脂肪酸诱导的死亡。这些数据还可能为探索二甲双胍治疗非酒精性脂肪肝疾病提供进一步的理论依据，揭示其对饱和脂肪酸引起的肝脏胰岛素抵抗的阻断作用。
The excessive supply of fatty acids to the liver contributes to hepatic insulin resistance and endoplasmic reticulum (ER) stress associated with obesity or type 2 diabetes mellitus. Furthermore, excess and/or prolonged ER stress contributes to hepatic cell death deteriorating nonalcoholic fatty liver disease to steatohepatitis. The aim of this study was to investigate the effects of metformin on palmitate-induced ER stress and hepatic insulin resistance in HepG2 cells. Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation. Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1. Metformin may therefore protect hepatocytes from death induced by saturated fatty acids. These data may also provide a further rationale for exploring the use of metformin in the treatment of non-alcoholic fatty liver disease, revealing its blocking effect for hepatic insulin resistance evoked by saturated fatty acids.