Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, Jiangsu, People's Republic of China.
Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Chiba 274-8555, Japan.
Environ Toxicol Pharmacol. 2019 Jul;69:66-71. doi: 10.1016/j.etap.2019.04.001. Epub 2019 Apr 2.
The therapeutic use of silk-derived materials such as fibroin in biomedicine is well-established in Southeast Asian countries. Studies indicated that silk fibroin (SF) peptide enhances insulin sensitivity and glucose metabolism phenomena associated with type 2 diabetes mellitus (T2DM) suggesting this peptide may be beneficial to treat this disease. However, the mechanisms underlying protective effect of SF in insulin-mediated hepatic metabolic dysfunction remains unclear. The aim of this study was to investigate the influence of SF on insulin resistant HepG2 cells which were used a model of T2DM. Treatment of cells with 30 mmol/L of glucose and 10 mol/L insulin for 48 h significantly reduced glucose consumptions and intracellular glycogen levels but increased triglyceride (TG) levels. SF or metformin alone elevated glucose consumptions and glycogen accumulation accompanied by lower TG content. Greater effects in these metabolic parameters were found when SF and metformin were combined. Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased. The combination of SF and metformin produced greater changes in these parameters compared to metformin alone. Data indicated that the protective effect of SF or metformin in insulin resistant HepG2 cells involves inhibition of oxidant processes and that the combination of agents may prove more effective therapeutically.
丝素衍生材料（如丝素蛋白）在生物医药中的治疗用途在东南亚国家已得到广泛应用。研究表明，丝素（SF）肽可增强与 2 型糖尿病（T2DM）相关的胰岛素敏感性和葡萄糖代谢现象，表明该肽可能有益于治疗这种疾病。然而，SF 在胰岛素介导的肝代谢功能障碍中的保护作用的机制尚不清楚。本研究旨在研究 SF 对胰岛素抵抗 HepG2 细胞的影响，该细胞被用作 T2DM 的模型。用 30mmol/L 葡萄糖和 10mol/L 胰岛素处理细胞 48h 可显著降低葡萄糖消耗和细胞内糖原水平，但增加甘油三酯（TG）水平。SF 或二甲双胍单独使用可提高葡萄糖消耗和糖原积累，同时 TG 含量降低。当 SF 和二甲双胍联合使用时，这些代谢参数的效果更大。SF 或二甲双胍单独处理胰岛素抵抗细胞可降低活性氧（ROS）、丙二醛（MDA）、肿瘤坏死因子（TNF-α）和白细胞介素-6（IL-6）水平；而抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及总抗氧化能力（T-AOC）能力增加。与单独使用二甲双胍相比，SF 和二甲双胍联合使用在这些参数上产生了更大的变化。数据表明，SF 或二甲双胍在胰岛素抵抗 HepG2 细胞中的保护作用涉及抑制氧化过程，并且联合使用这些药物可能在治疗上更有效。
