Upregulation of vitamin D-binding protein is associated with changes in insulin production in pancreatic beta-cells exposed to p,p′-DDT and p,p′-DDE

Abstract

AbstractPersistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment. Some studies have described a correlation between the level of POPs in the human body and the incidence of diabetes, but we know little about the direct effect of POPs on pancreatic beta-cells. We exposed pancreatic beta-cells INS1E to non-lethal concentrations of p,p′-DDT (1,1′-(2,2,2-Trichloroethane-1,1-diyl)bis(4-chlorobenzene)) and p,p′-DDE (1,1′-(2,2-dichloroethene-1,1-diyl)bis(4-chlorobenzene)) for 1 month, and assessed changes in protein expression and the intracellular insulin level. 2-D electrophoresis revealed 6 proteins with changed expression in cells exposed to p,p′-DDT or p,p′-DDE. One of the detected proteins – vitamin D-binding protein (VDBP) – was upregulated in both cells exposed to p,p′-DDT, and cells exposed to p,p′-DDE. Both exposures to pollutants reduced the intracellular level of insulin mRNA, proinsulin, and insulin monomer; p,p′-DDT also slightly reduced the level of hexameric insulin. Overexpression of VDBP caused by the stable transfection of beta-cells with the gene for VDBP decreased both the proinsulin and hexameric insulin level in beta-cells similarly to the reduction detected in cells exposed to p,p′-DDT. Our data suggest that in the cells exposed to p,p′-DDT and p,p′-DDE, the increased VDBP protein level decreased the proinsulin expression in an unknown mechanism.