Molecular dissection of cellular response of pancreatic islet cells to Bisphenol-A (BPA): A comprehensive review

Bisphenol A (BPA) is an endocrine disrupting chemical which poses great concern because of its high proportionate industrial production, omnipresent human exposure and budding toxic consequences in human. A plethora of previous studies has connected BPA to a variety of negative health outcomes and diabetes mellitus is among the first bencher. However, there is disagreement over the degree of toxic effects generated by low and high doses of BPA and critical period of exposure. Furthermore, the safe level of BPA determined by classical toxicological studies does not protect pancreatic islet cells from low dose effects of BPA. Thus, the extremities of toxic effects on pancreatic islets associated with BPA exposure are complicated and contentious. In this review, we highlighted different cellular and molecular pathways targeted by BPA to mediate its action on pancreatic islets with consideration of both low and high dose effects. Besides estrogen receptor alpha and 13, BPA also uses non canonical membrane bound estrogen receptor and G-protein coupled estrogen receptor to confer its toxic effects. In doing so, BPA modulates ion channels, and transcription factors; causes aggregation of human islet amyloid polypeptide, endoplasmic reticulum and mitochondrial stress; and results in activation of NFxB in pancreatic 13 cells. BPA also renders a major shift in 13 to alpha cell ratio in islets causing deregulated glucagon secretion. Hence, understanding of various mechanisms of BPA action on the pancreatic islets will provide meaningful insights in recognizing the risk posed by exposure to low and high doses of BPA.

Automated summary

Bisphenol A (BPA) is an endocrine disrupting chemical that is widely present in industrial production and has potential harmful effects on human health. This review focuses on the different cellular and molecular pathways through which BPA affects pancreatic islets, considering both low and high dose effects. Understanding the mechanisms of BPA action on pancreatic islets provides meaningful insights into the risks associated with exposure to BPA at different doses.