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
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31792309
PubMed Central
PMC6889289
DOI
10.1038/s41598-019-54579-z
PII: 10.1038/s41598-019-54579-z
Knihovny.cz E-resources
- MeSH
- Insulin-Secreting Cells drug effects metabolism MeSH
- Cell Line MeSH
- DDT toxicity MeSH
- Dichlorodiphenyl Dichloroethylene toxicity MeSH
- Insulin metabolism MeSH
- Rats MeSH
- Environmental Pollutants toxicity MeSH
- Vitamin D-Binding Protein metabolism MeSH
- Toxicity Tests, Subchronic MeSH
- Up-Regulation drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DDT MeSH
- Dichlorodiphenyl Dichloroethylene MeSH
- Insulin MeSH
- Environmental Pollutants MeSH
- Vitamin D-Binding Protein MeSH
Persistent 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.
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