Journal
TOXICOLOGY LETTERS
Volume 295, Issue -, Pages 162-172Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.06.1071
Keywords
Bisphenol A; Calcium homeostasis; Diabetes; ER stress; Octylphenol
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Funding
- National Research Foundation of Korea (NRF) from Korean government (MEST) [2017R1A2B2005031]
- National Research Foundation of Korea [2017R1A2B2005031] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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In pancreatic ji cells, which produce and secrete insulin, Ca2 signals contribute to insulin production and secretion. Bisphenol A (BPA) and octylphenol (OP) are reported to increase plasma insulin levels and insulin transcription factors, but regulation of plasma glucose levels did not decrease proportionally to the insulin increase. We hypothesized that BPA and OP disrupt calcium homeostasis resulting in insulin resistance through induction of endoplasmic reticulum (ER) stress. BPA and OP treatment leads to survival of pancreatic ji cells against streptozotocin, but despite an increased insulin level, serum glucose regulation is not properly regulated. The expression of genes involved in transporting calcium ions to the cytosol and ER decreased while the expression of those affecting the removal of calcium from the cytosol and ER increased. Depletion of calcium from the ER leads to ER stress and can induce insulin resistance. Insulin resistance is also confirmed by insulin responsive gene, such as glucose transporter 4 (GLUT4) and IRS2, expression. Taken together, these results imply that disruption of calcium homeostasis by BPA and OP induces ER stress and leads to insulin resistance, especially in a streptozotocin (STZ)-induced type 1 diabetes mellitus model.
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