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Toxicol Lett. 2018 Oct 1;295:162-172. doi: 10.1016/j.toxlet.2018.06.1071. Epub 2018 Jun 20.

Bisphenol A and octylphenol exacerbate type 1 diabetes mellitus by disrupting calcium homeostasis in mouse pancreas.

Author information

1
Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644 Republic of Korea.
2
Laboratory of Veterinary Biochemistry, College of Veterinary Medicine, Chungnam National University, Daejeon, 34134 Republic of Korea.
3
Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644 Republic of Korea. Electronic address: ebjeung@chungbuk.ac.kr.

Abstract

In pancreatic β 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 β 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.

KEYWORDS:

Bisphenol A; Calcium homeostasis; Diabetes; ER stress; Octylphenol

PMID:
29935216
DOI:
10.1016/j.toxlet.2018.06.1071
[Indexed for MEDLINE]

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