Marine Bromophenol Derivative 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol Protects Hepatocytes from Lipid-Induced Cell Damage and Insulin Resistance via PTP1B Inhibition.
Marine Bromophenol Derivative 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol Protects Hepatocytes from Lipid-Induced Cell Damage and Insulin Resistance via PTP1B Inhibition.
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DOI：
10.3390/md13074452
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发表时间：
2015-07-17
期刊：
影响因子：
5.4
通讯作者：
Shi D
中科院分区：
文献类型：
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作者：
Luo J;Wu N;Jiang B;Wang L;Wang S;Li X;Wang B;Wang C;Shi D
苯基苯-1，2-二醇(3，4-Dibromo-5-(2-bromo-3，4-dihydroxy-6-isopropoxymethyl-1，2-diol，HPN)是从海洋红藻红藻中提取的一种溴苯酚衍生物。我们先前在db/db小鼠模型中发现HPN具有降血糖作用。在本研究中，我们发现HPN可以保护HepG2细胞免受棕榈酸酯(PA)诱导的细胞死亡。数据还表明，HPN主要通过阻断细胞凋亡来抑制细胞死亡。进一步的研究表明，HPN(尤其是1.0μM)能显著恢复胰岛素刺激的IR和IRS1/2的酪氨酸磷酸化，并抑制PTP1B的表达水平。此外，HPN还能激活Akt的表达，并显著增加PA处理的HepG2细胞对葡萄糖的摄取。提示HPN可能通过抑制PTP1B而保护肝细胞免受脂质诱导的细胞损伤和胰岛素抵抗。因此，HPN有潜力开发出既能保护肝细胞质量又能保护肝细胞功能的抗糖尿病药物。
3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol (HPN) is a bromophenol derivative from the marine red alga Rhodomela confervoides. We have previously found that HPN exerted an anti-hyperglycemic property in db/db mouse model. In the present study, we found that HPN could protect HepG2 cells against palmitate (PA)-induced cell death. Data also showed that HPN inhibited cell death mainly by blocking the cell apoptosis. Further studies demonstrated that HPN (especially at 1.0 μM) significantly restored insulin-stimulated tyrosine phosphorylation of IR and IRS1/2, and inhibited the PTP1B expression level in HepG2 cells. Furthermore, the expression of Akt was activated by HPN, and glucose uptake was significantly increased in PA-treated HepG2 cells. Our results suggest that HPN could protect hepatocytes from lipid-induced cell damage and insulin resistance via PTP1B inhibition. Thus, HPN can be considered to have potential for the development of anti-diabetic agent that could protect both hepatic cell mass and function.