Oleuropein attenuates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-perturbing effects on pancreatic β-cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E2 (PGE2 ) compared to the untreated control, and this increase was inhibited by oleuropein treatment. TCDD increased Ca2+ -independent phospholipase A2 (iPLA2 β) level, but had no effect on Group 10 secretory phospholipase A2 (PLA2 G10) level, while oleuropein deceased the levels of iPLA2 β and PLA2 G10 in the presence of TCDD. Cyclooxygenase-1 (COX-1) was significantly increased by TCDD treatment and attenuated with oleuropein pretreatment. Oleuropein decreased TCDD-mediated production of JNK, TNF-α, and ROS. In addition, oleuropein increased Akt and GLUT2 levels suppressed by TCDD in INS-1 cells. Thus, the results suggest that oleuropein prevents pancreatic beta cell impairment by TCDD.