PMID- 31792309
OWN - NLM
STAT- MEDLINE
DCOM- 20201113
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Dec 2
TI  - 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.
PG  - 18026
LID - 10.1038/s41598-019-54579-z [doi]
LID - 18026
AB  - 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.
FAU - Pavlikova, Nela
AU  - Pavlikova N
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic. nela.pavlikova@lf3.cuni.cz.
FAU - Daniel, Petr
AU  - Daniel P
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
FAU - Sramek, Jan
AU  - Sramek J
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
FAU - Jelinek, Michael
AU  - Jelinek M
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
FAU - Sramkova, Veronika
AU  - Sramkova V
AD  - Department of Pathophysiology & Center for Research of Diabetes, Metabolism, and 
      Nutrition, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
FAU - Nemcova, Vlasta
AU  - Nemcova V
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
FAU - Balusikova, Kamila
AU  - Balusikova K
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
FAU - Halada, Petr
AU  - Halada P
AD  - Laboratory of Molecular Structure Characterization, Institute of Microbiology of 
      the Czech Academy of Sciences, Prague, Czech Republic.
FAU - Kovar, Jan
AU  - Kovar J
AD  - Department of Biochemistry, Cell and Molecular Biology & Center for Research of 
      Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles 
      University, Prague, Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191202
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Environmental Pollutants)
RN  - 0 (Insulin)
RN  - 0 (Vitamin D-Binding Protein)
RN  - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene)
RN  - CIW5S16655 (DDT)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DDT/toxicity
MH  - Dichlorodiphenyl Dichloroethylene/toxicity
MH  - Environmental Pollutants/*toxicity
MH  - Insulin/*metabolism
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Rats
MH  - Toxicity Tests, Subchronic
MH  - Up-Regulation/drug effects
MH  - Vitamin D-Binding Protein/*metabolism
PMC - PMC6889289
COIS- The authors declare no competing interests.
EDAT- 2019/12/04 06:00
MHDA- 2020/11/18 06:00
PMCR- 2019/12/02
CRDT- 2019/12/04 06:00
PHST- 2019/02/27 00:00 [received]
PHST- 2019/11/12 00:00 [accepted]
PHST- 2019/12/04 06:00 [entrez]
PHST- 2019/12/04 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/12/02 00:00 [pmc-release]
AID - 10.1038/s41598-019-54579-z [pii]
AID - 54579 [pii]
AID - 10.1038/s41598-019-54579-z [doi]
PST - epublish
SO  - Sci Rep. 2019 Dec 2;9(1):18026. doi: 10.1038/s41598-019-54579-z.