Nickel Sulfate-Induced GSIS Injury in MIN6 Cells by Activating the JNK Pathway Through Oxidative Stress

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 (NiSO₄) (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). NiSO₄ damaged MIN6 cells in a time- and dose-dependent manner. NiSO₄ blocked the cell cycle, induced apoptosis, and reduced insulin secretion in the GSIS experiment. NiSO₄ 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, NiSO₄ activated the JNK pathway, upregulated FOXO1 protein expression, and inhibited PDX-1 and GLUT2 protein expression, affecting insulin release during GSIS. NiSO₄ 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.