Toktay Erdem, Parlak Secil Nazife, Kavas Tugba, Un Harun, Ugan Rustem Anıl, Yayla Muhammed
Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars 36000, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Agri Ibrahim Cecen University, Agri 04100, Turkey.
Curr Issues Mol Biol. 2025 Jul 10;47(7):535. doi: 10.3390/cimb47070535.
In this study, we aimed to investigate the effect of Engeletin (ENG) on insulin resistance and the associated oxidative cell damage in human HepG2 liver cells. The cells were grown in a cell culture medium, and insulin resistance was induced. After the determination of the toxic and effective doses of Engeletin, the effects of Engeletin on insulin resistance and insulin resistance-induced oxidative damage, inflammation, and apoptosis. To induce IR, culture plates were treated with 30 mM glucose and 50 nM insulin and incubated for 48 h. Engeletin and metformin were given one hour before starting the insulin resistance induction. In the HepG2 cells, insulin resistance decreased glucose consumption, the expression of ISR-1 and ISR-2, and the GLUT-2 levels, while they were all increased by Engeletin, which showed a metformin-like effect. In addition, Engeletin alleviated oxidative cell damage by decreasing MDA levels, which increased due to insulin resistance-induced oxidative stress, increasing the GSH and SOD levels and decreasing the caspase-3 (Cas-3), caspase-9 (Cas-9), and tumor necrosis factor alpha (TNF-α) levels, which also increase under insulin resistance conditions. Engeletin was found to have the protective and therapeutic effect of reducing insulin resistance (IR) and the oxidative cell damage it causes in human HepG2 cells.
在本研究中,我们旨在探讨恩格列净(ENG)对人肝癌细胞系HepG2中胰岛素抵抗及相关氧化细胞损伤的影响。细胞在细胞培养基中培养,并诱导产生胰岛素抵抗。在确定恩格列净的毒性和有效剂量后,研究了其对胰岛素抵抗以及胰岛素抵抗诱导的氧化损伤、炎症和细胞凋亡的影响。为诱导胰岛素抵抗,将培养板用30 mM葡萄糖和50 nM胰岛素处理,并孵育48小时。在开始诱导胰岛素抵抗前1小时给予恩格列净和二甲双胍。在HepG2细胞中,胰岛素抵抗降低了葡萄糖消耗、ISR-1和ISR-2的表达以及GLUT-2水平,而恩格列净使其均升高,显示出类似二甲双胍的作用。此外,恩格列净通过降低丙二醛(MDA)水平减轻氧化细胞损伤,MDA水平因胰岛素抵抗诱导的氧化应激而升高,恩格列净还增加了谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平,并降低了半胱天冬酶-3(Cas-3)、半胱天冬酶-9(Cas-9)和肿瘤坏死因子α(TNF-α)水平,这些指标在胰岛素抵抗条件下也会升高。研究发现恩格列净具有降低胰岛素抵抗(IR)及其在人HepG2细胞中引起的氧化细胞损伤的保护和治疗作用。