Department of applied science, school of pharmacy, University of Brighton, BN24GJ, UK.
Department of applied science, school of pharmacy, University of Brighton, BN24GJ, UK.
J Diabetes Complications. 2024 Sep;38(9):108832. doi: 10.1016/j.jdiacomp.2024.108832. Epub 2024 Aug 5.
Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer's disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50-75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.
糖尿病是一种由胰岛素作用或分泌功能障碍引起的代谢紊乱，导致血糖水平升高。它是一种高发疾病，因此国民保健制度（NHS）将其全部预算的 10%用于糖尿病护理，即每年 100 亿英镑。糖尿病与血管和神经并发症有关，这些并发症可能与神经退行性变和阿尔茨海默病的进展有关。慢性高血糖会增加活性氧（ROS）的产生，如甲基乙二醛（MGO）。MGO 与血管并发症、神经病变和细胞毒性有关。本研究的主要目的是研究二甲双胍和达格列净等抗糖尿病药物对 MGO 处理的人脑神经细胞（SH-SY5Y）的潜在有益作用。SH-SY5Y 细胞在 DMEM/F12 培养基中培养，并在以下一种处理条件下过夜孵育：对照（未处理）；MGO（1 μM）；MGO（100 μM）；二甲双胍（100 μM）+MGO（100 μM）；和达格列净（10 μM）+MGO（100 μM）。进行了几项测定来探索治疗组对 SH-SY5Y 细胞的影响。这些测定包括：MTT 测定；LDH 测定、过氧亚硝酸盐荧光测定和激光扫描共聚焦显微镜。MGO（100 μM）导致显著的细胞损伤和损伤，使细胞存活率显著降低约 50-75%，同时过氧亚硝酸盐显著增加。二甲双胍（100 μM）或达格列净（10 μM）的添加对细胞具有显著的保护作用，并防止了高浓度 MGO 引起的细胞损伤。因此，这项研究的结果表明，MGO 诱导的细胞损伤可能部分是通过过氧亚硝酸盐的产生介导的，而二甲双胍和达格列净等抗糖尿病药物可防止脑细胞死亡，这可能对糖尿病患者痴呆风险起到预防作用。
