Sun Bo, Chen Hui
Endocrine and Metabolism Department, Lanzhou University Second Hospital, Chengguan District, No. 82, CuyingmenLanzhou, 730000, Gansu, China.
Department of Infantile Endocrine Genetic Metabolism, Gansu Maternal and Child Health Care Hospital, Lanzhou, 730000, Gansu, China.
Biol Trace Elem Res. 2024 Dec 11. doi: 10.1007/s12011-024-04477-x.
Nickel has an impact on human health, especially in the context of the new energy industries. Nickel's influence on glycemia remains controversial, and the effects and mechanisms of nickel on islet function still need further exploration. MIN6 cells were treated with different concentrations of nickel sulfate (NiSO) (0, 75, 150, and 300 µg/mL) for different durations (0, 12, 24, and 48 h). The study measured cell cycle progression, apoptosis, reactive oxygen species (ROS) production, oxidative stress-related indexes (T-SOD, TBARS, 8-OHdG, and GSH), glucose-induced insulin secretion (GSIS), and the expression of JNK pathway-related proteins, pancreaticoduodenal homeobox-1 (PDX-1), glucose transporter 2 (GLUT2), and forkhead box protein O1 (FOXO1). NiSO damaged MIN6 cells in a time- and dose-dependent manner. NiSO blocked the cell cycle, induced apoptosis, and reduced insulin secretion in the GSIS experiment. NiSO also induced ROS production, increased oxidative stress-related indexes (TRABS and 8-OHdG), and decreased antioxidant stress-related indexes (GSH and T-SOD). In addition, NiSO activated the JNK pathway, upregulated FOXO1 protein expression, and inhibited PDX-1 and GLUT2 protein expression, affecting insulin release during GSIS. NiSO inhibited the proliferation of MIN6 cells through oxidative stress, aggravated apoptosis, caused functional impairment, upregulated the expression of FOXO1 by activating the JNK pathway, inhibited the expression of PDX-1 and GLUT2 proteins, and impaired the GSIS function of islets.
镍对人类健康有影响，特别是在新能源产业背景下。镍对血糖的影响仍存在争议，其对胰岛功能的作用及机制仍需进一步探索。将MIN6细胞用不同浓度的硫酸镍（NiSO）（0、75、150和300μg/mL）处理不同时长（0、12、24和48小时）。该研究检测了细胞周期进程、细胞凋亡、活性氧（ROS）生成、氧化应激相关指标（总超氧化物歧化酶、丙二醛、8-羟基脱氧鸟苷和谷胱甘肽）、葡萄糖刺激的胰岛素分泌（GSIS）以及JNK通路相关蛋白、胰十二指肠同源盒-1（PDX-1）、葡萄糖转运蛋白2（GLUT2）和叉头框蛋白O1（FOXO1）的表达。硫酸镍以时间和剂量依赖性方式损伤MIN6细胞。在GSIS实验中，硫酸镍阻滞细胞周期、诱导细胞凋亡并减少胰岛素分泌。硫酸镍还诱导ROS生成，增加氧化应激相关指标（丙二醛和8-羟基脱氧鸟苷），并降低抗氧化应激相关指标（谷胱甘肽和总超氧化物歧化酶）。此外，硫酸镍激活JNK通路，上调FOXO1蛋白表达，并抑制PDX-1和GLUT2蛋白表达，影响GSIS过程中的胰岛素释放。硫酸镍通过氧化应激抑制MIN6细胞增殖，加重细胞凋亡，导致功能受损，通过激活JNK通路上调FOXO1表达，抑制PDX-1和GLUT2蛋白表达，并损害胰岛的GSIS功能。
