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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

N. Pavlíková, P. Daniel, J. Šrámek, M. Jelínek, V. Šrámková, V. Němcová, K. Balušíková, P. Halada, J. Kovář,

. 2019 ; 9 (1) : 18026. [pub] 20191202

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

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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$a Persistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment. Some studies have described a correlation between the level of POPs in the human body and the incidence of diabetes, but we know little about the direct effect of POPs on pancreatic beta-cells. We exposed pancreatic beta-cells INS1E to non-lethal concentrations of p,p'-DDT (1,1'-(2,2,2-Trichloroethane-1,1-diyl)bis(4-chlorobenzene)) and p,p'-DDE (1,1'-(2,2-dichloroethene-1,1-diyl)bis(4-chlorobenzene)) for 1 month, and assessed changes in protein expression and the intracellular insulin level. 2-D electrophoresis revealed 6 proteins with changed expression in cells exposed to p,p'-DDT or p,p'-DDE. One of the detected proteins - vitamin D-binding protein (VDBP) - was upregulated in both cells exposed to p,p'-DDT, and cells exposed to p,p'-DDE. Both exposures to pollutants reduced the intracellular level of insulin mRNA, proinsulin, and insulin monomer; p,p'-DDT also slightly reduced the level of hexameric insulin. Overexpression of VDBP caused by the stable transfection of beta-cells with the gene for VDBP decreased both the proinsulin and hexameric insulin level in beta-cells similarly to the reduction detected in cells exposed to p,p'-DDT. Our data suggest that in the cells exposed to p,p'-DDT and p,p'-DDE, the increased VDBP protein level decreased the proinsulin expression in an unknown mechanism.
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$a Daniel, Petr $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Šrámek, Jan $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Jelínek, Michael $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Šrámková, Veronika $u Department of Pathophysiology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Němcová, Vlasta $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Balušíková, Kamila $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Halada, Petr $u Laboratory of Molecular Structure Characterization, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
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$a Kovář, Jan $u Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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