A1 Refereed original research article in a scientific journal
Chronic Bisphenol ‐ A Exposure Enhances ROS and AGEs Production via the RAGE/PI3K/AKT/mTOR Signaling Pathway, Inducing Apoptosis in Human Pancreatic β‐Cells
Authors: Anastasiou, Ioanna A.; Tentolouris, Anastasios; Sarantis, Panagiotis; Rebelos, Eleni; Eleftheriadou, Ioanna; Tentolouris, Nikolaos,
Publisher: Wiley
Publication year: 2025
Journal: Journal of Biochemical and Molecular Toxicology
Article number: e70569
Volume: 39
Issue: 11
ISSN: 1095-6670
eISSN: 1099-0461
DOI: https://doi.org/10.1002/jbt.70569
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1002/jbt.70569
Type 2 diabetes mellitus (T2D) is characterized by insulin resistance and a progressive decline in pancreatic β-cell function. Bisphenol-A (BPA), an industrial chemical widely used in manufacturing plastics and resins, is known to disrupt endocrine function and impair pancreatic β-cell activity. This study aims to investigate the effects of chronic exposure to low concentrations of BPA on pancreatic β-cells and to elucidate the underlying molecular mechanisms involved. 1.2B4 cells (RRID: CVCL_2258) were cultured in medium containing BPA at concentrations of 0.0002, 0.002, 0.01, and 0.02 μM for 7 days. Cellular outcomes measured included viability, apoptosis, ATP levels, and proliferation. Insulin secretion and content were also assessed as indicators of β-cell function. Additionally, levels of intracellular reactive oxygen species (ROS), advanced glycation end-products (AGEs), and soluble receptor for AGEs (sRAGE) were quantified. Apoptosis markers and gene expression related to apoptotic pathways were analyzed using quantitative real-time PCR (qRT-PCR). The involvement of specific signaling pathways, such as RAGE/PI3K/AKT/mTOR, was investigated. BPA exposure markedly inhibited proliferation and growth of 1.2B4 cells, with a reduction of up to 50% compared to controls, indicating potent antiproliferative effects. BPA also increased ROS and AGEs production through activation of the RAGE/PI3K/AKT/mTOR pathway, leading to enhanced apoptosis. The data suggest that low-dose BPA induces mitochondrial apoptosis in pancreatic β-cells in a dose-dependent manner, mediated by oxidative stress and AGE accumulation. Chronic exposure to low concentrations of BPA impairs pancreatic β-cell viability and function by promoting oxidative stress and apoptosis via RAGE-dependent signaling cascades. These findings highlight the potential health risks associated with BPA exposure and underscore its possible role in β-cell dysfunction related to T2D development.
Funding information in the publication:
The authors received no specific funding for this work.
