Tripterine Serves a Dual Role in Palmitate-Induced Pancreatic Beta-Cell Lipotoxicity

Tripterine (TP, also called celastrol), a pentacyclic triterpene extracted from Tripterygium wilfordii, has beneficial effects on multiple diseases, including obesity and diabetes. However, the effects of TP on beta-cell lipotoxicity have not been fully explored. Here, we found that TP modulated beta-cell lipotoxicity in a concentration-dependent and bidirectional manner. At low concentrations, TP potentially protected MIN6 beta-cells from palmitate (PA)-induced lipotoxicity. At high concentrations, TP significantly promoted beta-cell lipotoxicity, further reinforcing PA-induced cell apoptosis. Furthermore, low-concentration TP inhibited the PA-induced increase in reactive oxygen species (ROS) levels, and its protective effects were abolished by the ROS inducer tert-butyl hydroperoxide. Conversely, high-concentration TP significantly exacerbated the PA-triggered ROS generation, and its enhanced cytotoxicity was partially reversed by the ROS inhibitor N-acetyl-L-cysteine. Thus, TP plays a dual role in beta-cell lipotoxicity, suggesting that care should be taken when it is used for obesity and diabetes treatment.