MIN6

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 new energy industries. Nickel's influence on glycemia remains controversial, and the effect and mechanism 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.

Fig. 1. NiSO₄ reduced the viability of MIN6 cells, blocked the cell cycle in the G0/G1 phase, induced cell apoptosis, and caused damage to the function of islet cells (Sun, Bo, and Hui Chen. 2024).

Fig. 2. NiSO₄ activated the JNK pathway, upregulated FOXO1 protein expression, and inhibited PDX-1 and GLUT2 protein expression, resulting in decreased GSIS function of MIN6 cells (Sun, Bo, and Hui Chen. 2024).

Puerarin Ameliorates High Glucose-Induced MIN6 Cell Injury by Activating PINK1/Parkin-Mediated Mitochondrial Autophagy

The dysfunction of pancreatic β-cells plays a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite numerous studies have demonstrated the anti-inflammatory and antioxidant properties of puerarin, the protective effects of puerarin on β-cells remain poorly understood. Hence, this study aimed to explore the effects of puerarin on β-cell dysfunction in a hyperglycemic environment via the PINK/Parkin-mediated mitochondrial autophagy pathway.

MIN6 cells were exposed to glucose concentrations of 5 mM, 10 mM, 20 mM, and 30 mM for 24 h, 48 h, and 72 h, respectively. Results indicated a significant decrease in MIN6 cell viability following 48 h of exposure to 30 mM glucose concentration. Puerarin intervention markedly attenuated ROS production, restored mitochondrial membrane potential, induced PINK/Parkin-mediated mitochondrial autophagy, suppressed activation of the mitochondrial apoptotic pathway, mitigated apoptosis, and enhanced insulin secretion in a high glucose (HG) environment. The findings of this investigation contribute to a deeper understanding of the precise mechanism underlying the protective effects of puerarin on β-cells and offer a theoretical foundation for advancing puerarin-based therapeutics aimed at ameliorating T2DM.

Fig. 3. Effect of different concentrations of glucose and time on the viability values of MIN6 cells (Zhu, Hongyang, et al. 2024).

Fig. 4. Puerarin enhances PINK1/Parkin-mediated mitochondrial autophagy in HG-induced MIN6 cells (Zhu, Hongyang, et al. 2024).