1. BDE-47 and BDE-85 stimulate insulin secretion in INS-1 832/13 pancreatic β-cells through the thyroid receptor and Akt.
- Author
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Karandrea S, Yin H, Liang X, and Heart EA
- Subjects
- Cell Line, Gene Expression Regulation drug effects, Halogenated Diphenyl Ethers toxicity, Humans, Insulin Secretion, Insulin-Secreting Cells cytology, Insulin-Secreting Cells drug effects, Proto-Oncogene Proteins c-akt metabolism, Receptors, Thyroid Hormone metabolism, Signal Transduction drug effects, Environmental Pollutants toxicity, Glucose pharmacology, Insulin metabolism, Insulin-Secreting Cells metabolism
- Abstract
PBDEs (polybrominated diphenyl ethers) are environmental pollutants that have been linked to the development of type 2 diabetes, however, the precise mechanisms are not clear. Particularly, their direct effect on insulin secretion is unknown. In this study, we show that two PBDE congeners, BDE-47 and BDE-85, potentiate glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells. This effect of BDE-47 and BDE-85 on GSIS was dependent on thyroid receptor (TR). Both BDE-47 and BDE-85 (10μM) activated Akt during an acute exposure. The activation of Akt by BDE-47 and BDE-85 plays a role in their potentiation of GSIS, as pharmacological inhibition of PI3K, an upstream activator of Akt, significantly lowers GSIS compared to compounds alone. This study shows that BDE-47 and BDE-85 directly act on pancreatic β-cells to stimulate GSIS, and that this effect is mediated by the thyroid receptor (TR) and Akt activation., (Copyright © 2017. Published by Elsevier B.V.)
- Published
- 2017
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