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Assessment of Arsenic-Induced Modifications in the Dna Methylation of Insulin-Related Genes in Rat Pancreatic Islets Publisher Pubmed



Khan F1 ; Hodjat M2 ; Rahimifard M1 ; Nigjeh MN1 ; Azizi M3 ; Baeeri M1 ; Bayrami Z1 ; Gholami M1 ; Hassani S1 ; Abdollahi M1
Authors
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Authors Affiliations
  1. 1. Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran
  2. 2. Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

Source: Ecotoxicology and Environmental Safety Published:2020


Abstract

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (−1743, −1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (β-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced β-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin. © 2020 Elsevier Inc.
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