Comprehensive investigation into the discrete toxicity of curcumin on β-cell viability and insulin secretion

Curcumin possesses several therapeutic benefits. However, the precise mechanisms underlying these actions have not been fully elucidated. The aim of this study was to highlight the toxic effects on β-cells and islets.

The toxic effects of curcumin were investigated on cell viability in ALB/c mouse-isolated Langerhans islets and NIT1 cells (CRL-2055™, a NOD mouse β cell line), and insulin secretion. We evaluated its effects on oxidative stress markers, ROS production, and its role in ER stress through the stimulation of three genes involved in the UPR response. In silico and in vitro studies were conducted to extract a set of genes and curcumin-PPI using a multistep pipeline.

Curcumin increases cell viability and insulin secretion in islets of Langerhans. At 60 μg/mL (0,163 μM), curcumin affected β-cell viability, reducing it by up to 70-75 %, and significantly reduced insulin secretion. It also induces oxidative stress and increases the expression of NFKB1, ATF4, and CHOP. These effects were enhanced when curcumin was combined with STZ. Bioinformatic studies have indicated that curcumin interacts with 14 proteins, including Jund, Ddit3, Dapk3, Cebpa, and the NFkB pathway through NFkBia.

At high concentrations, curcumin is cytotoxic. It induces β-cell apoptosis associated with UPR-ER and oxidative stress, implicating the NFkB pathway and its associated proteins.