School of Public Health, Qingdao University, Qingdao 266071, China.
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China.
Mar Drugs. 2020 May 19;18(5):267. doi: 10.3390/md18050267.
3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga . Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was embedded into the catalytic pocket of PTP1B. A cellular study found that CYC31 increased the activity of insulin signaling and promoted 2-NBDG uptake through GLUT4 translocation in C2C12 myotubes. Further studies showed that CYC31 ameliorated palmitate-induced insulin resistance in C2C12 myotubes. Moreover, CYC31 treatment significantly increased the mRNA expression of carnitine palmitoyltransferase 1B () and fatty acid binding protein 3 (), which was tightly linked with fatty acid oxidation. These findings suggested that CYC31 could prevent palmitate-induce insulin resistance and could improve fatty acid oxidation through PTP1B inhibition.
3-溴-4,5-双（2,3-二溴-4,5-二羟基苯甲基）-1,2-苯二酚（CYC31）是从红藻中分离出的一种溴酚蛋白酪氨酸磷酸酶 1B（PTP1B）抑制剂。本文研究了 CYC31 对 C2C12 肌管胰岛素信号和脂肪酸诱导紊乱的影响。分子对接试验表明，CYC31 嵌入 PTP1B 的催化口袋中。细胞研究发现，CYC31 通过 GLUT4 易位增加 C2C12 肌管中的胰岛素信号活性并促进 2-NBDG 摄取。进一步的研究表明，CYC31 改善了 C2C12 肌管中棕榈酸诱导的胰岛素抵抗。此外，CYC31 处理显著增加了肉毒碱棕榈酰转移酶 1B（）和脂肪酸结合蛋白 3（）的 mRNA 表达，这与脂肪酸氧化密切相关。这些发现表明，CYC31 可通过抑制 PTP1B 预防棕榈酸诱导的胰岛素抵抗，并可改善脂肪酸氧化。
