壳寡糖(chitooligosaccharides, COS)是一种具有多种生物活性的低聚寡糖,该文探究了COS对HepG2细胞胰岛素抵抗的影响作用。通过胰岛素诱导HepG2细胞建立胰岛素抵抗模型,评估COS及其单体组分(聚合度2~4)对其缓解作用。结果显示,COS显著提高产生胰岛素抵抗HepG2细胞的葡萄糖消耗量,促进其葡萄糖代谢。进一步评估不同聚合度的COS单体发现,壳二糖和壳四糖对胰岛素抵抗的肝细胞无显著改善效果,而壳三糖显著提高胰岛素抵抗HepG2细胞的葡萄糖消耗量。另外,COS及壳三糖显著提高胰岛素受体(insulin receptor, IR)、胰岛素受体底物 1(insulin receptor substrate 1, IRS-1)、葡萄糖转运蛋白4(glucose transporter 4, GLUT4)蛋白水平,活化蛋白激酶B(protein kinase B, PKB/Akt)以及改善相关基因转录水平。综上,COS通过介导Akt/GLUT4通路改善HepG2细胞的胰岛素抵抗,壳三糖在促进糖代谢中表现最优。
Chitooligosaccharides (COS) is an oligosaccharide with various biological activities. To explore the effects of COS and its monomer components (degrees of polymerization 2-4) on insulin resistance of hepatocytes, an insulin-resistant HepG2 cell model was established by insulin induction. The results showed that COS significantly enhanced the glucose consumption in insulin resistant HepG2 cells, suggesting that it promoted glucose metabolism of those cells. Further evaluation of the monomer components of COS exhibited that chitotriose obviously promoted the glucose consumption in insulin resistant HepG2 cells, while chitobiose and chitosan could not significantly show that ameliorative effect. Further mechanism analysis illustrated that COS and chitotriose increased the protein levels of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), glucose transporter 4 (GLUT4) and activated protein kinase B (PKB/Akt), while it improved the transcription level of related genes as well. Conclusively, COS improved the insulin resistant HepG2 cells by activating Akt/GLUT4 pathway, among which chitotriose showed excellent performance.
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