1772-P: Monocarbonyl Analogs of Curcumin C66 and B2BrBC Modulate Diabetes-Related Gene Expression in Rat Pancreatic Cells

Monocarbonyl analogs of curcumin (MACs) lacking a β-diketone moiety have been shown to exhibit improved stability and better bioavailability than curcumin. This study aimed to evaluate the effects of two MACs (C66 and B2BrBC) on the expression of genes related to the onset, development, and progression of diabetes in rat pancreatic RIN-m cells. The cells were cultured in complete RPMI 1640 medium and treated with C66 or B2BrBC (50 μM) or vehicle for 72 h, followed by treatment with streptozotocin (STZ) (1.5 mM) or vehicle for an additional 24 h. Quantitative PCR array analysis was performed using a rat diabetes panel comprising 84 genes. The data demonstrated that C66 and B2BrBC significantly modulated the expression of 16 genes involved in growth regulation in RIN-m cells and genes associated with inflammation, immune response, and energy metabolism. Notably, C66 and B2BrBC inhibited the STZ-induced expression of pro-inflammatory Tnf and Icam1 while increasing the expression of Ins1. Moreover, C66 pretreatment influenced Ctla4 and Serpine1 expression, and B2BrBC pretreatment affected Mapk8, Serpine1, and Igfbp5 levels compared to STZ treatment alone. Cells treated with MACs and STZ showed a different pattern of gene expression for Igfbp5, Gpd1, Agt, Serpine1, Cebpa, Retn, Ccl5, and Srebf1 compared to vehicle-treated cells. Our findings show that C66 and B2BrBC modulate the expression of essential diabetes-related genes, which may serve as a basis for further research on MACs and contribute to the development of novel therapeutic targets and strategies.