期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms24032023
关键词
unfolded protein response; diabetes; endocrine disruptor; bisphenol A; insulin granules
Diabetes, affecting nearly half a billion people worldwide, is linked to dysfunction of beta-cells. Exposure to endocrine-disrupting chemicals, such as bisphenol A (BPA), has been correlated with increased diabetes incidence. This study explores the activation of unfolded protein response (UPR) pathways in beta-cells under BPA treatment and the potential recovery of endoplasmic reticulum (ER) homeostasis. The findings suggest that modulators of UPR, like the chemical chaperone TUDCA, could be used as therapeutic interventions to restore beta-cell function.
Diabetes is a metabolic disease that currently affects nearly half a billion people worldwide. beta-cells dysfunction is one of the main causes of diabetes. Exposure to endocrine-disrupting chemicals is correlated with increased diabetes incidence. We hypothesized that treatment with bisphenol A (BPA) induces endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR), leading to impaired function of the beta-cells, which over time, can cause diabetes. In this study, we aimed to evaluate UPR pathways activation under BPA treatment in beta-cells and possible recovery of ER homeostasis. MIN6 cells (mouse insulinoma cell line) and isolated pancreatic islets from NOR (non-obese diabetes resistant) mice were treated with BPA. We analyzed the impact of BPA on beta-cell viability, the architecture of the early secretory pathway, the synthesis and processing of insulin and the activation of UPR sensors and effectors. We found that the addition of the chemical chaperone TUDCA rescues the deleterious effects of BPA, resulting in improved viability, morphology and function of the beta-cells. In conclusion, we propose that modulators of UPR can be used as therapeutic interventions targeted towards regaining beta-cells homeostasis.
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