RRC ID 65641
著者 Yokoyama K, Tatsumi Y, Hayashi K, Goto H, Ishikawa T, Wakusawa S.
タイトル Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity.
ジャーナル Biol Pharm Bull
Abstract In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate. The level of ROS was quantified using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), and the activation of the PI3K/Akt signaling pathway was determined by Western blotting assay using appropriate antibodies. The intracellular ROS levels were increased by palmitate but were reduced by treatment with UDCA and insulin. Furthermore, insulin significantly stimulated the phosphorylation of Akt. When the cells were pre-treated with palmitate, insulin-induced Akt-phosphorylation was markedly inhibited. However, when the cells were treated with palmitate and UDCA, the effects of insulin were partially restored. UDCA may have protective effects against palmitate-induced decreases in responsiveness to insulin.
巻・号 40(11)
ページ 2001-2004
公開日 2017-1-1
DOI 10.1248/bpb.b17-00423
PMID 29093351
MeSH Antioxidants / pharmacology* Down-Regulation Fatty Acids, Nonesterified / blood Fatty Acids, Nonesterified / metabolism Hep G2 Cells Humans Insulin / pharmacology* Insulin Resistance Intra-Abdominal Fat / metabolism Lipid Metabolism / drug effects Obesity / blood Obesity / metabolism Palmitates / metabolism Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Proto-Oncogene Proteins c-akt / metabolism Reactive Oxygen Species / metabolism* Signal Transduction / drug effects* Ursodeoxycholic Acid / pharmacology*
IF 1.863
リソース情報
ヒト・動物細胞 Hep G2