Implications of Antioxidant Enzyme Paraoxonase 2 in Insulin Synthesis and Secretion

The diabetes epidemic nowadays appeared at the same time with the obesity epidemic their relationship being a causal one. The protection offered by paraoxonase 2 (PON2), a recently discovered member of the paraoxonase multigene family that has been proposed to have antioxidant properties, is still a matter of debate. We aimed to investigate if antioxidant enzyme PON2 is affected by glucose (glucotoxicity) and lipids (lipotoxicity) levels in beta-pancreatic cells and if these, in turn, are related to functional changes in the synthesis and secretion of insulin. We determined the PON2 in beta-pancreatic cell lines INS-1 (rat) and PANC-1 (human). Cells (2X10(4) cells) were incubated with different concentrations of D-glucose (no glucose; hypo and hyperglycemia) in the presence or absence of either oleic acid (50 mu M), palmitic acid (1mM) or a mixture of them (oleate/palmitate:2/1). The cell lysates and media were separated by Tricine-SDS-PAGE and the insulin and PON2 were visualized by Western Blot and/or ELISA. With our model of in vitro islets, we showed that intracellular insulin accumulation was lower at higher glucose concentrations and this was associated with insulin secretion and PON2 changes in all cell lines studied. The effect was amplified by adding oleic acid in a combination with palmitic add. Our findings suggest that PON2 is present in beta-pancreatic cells and could protect against gluco and lipotoxicity being useful for prevention of type 2 diabetes obesity associated complications.