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 β‑cell lipotoxicity have not been fully explored. Here, we found that TP modulated β-cell lipotoxicity in a concentration-dependent and bidirectional manner. At low concentrations, TP potentially protected MIN6 β-cells from palmitate (PA)-induced lipotoxicity. At high concentrations, TP significantly promoted β-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 β-cell lipotoxicity, suggesting that care should be taken when it is used for obesity and diabetes treatment.