Karandrea Shpetim, Yin Huquan, Liang Xiaomei, Heart Emma A
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, 33612, United States.
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, 33612, United States.
Environ Toxicol Pharmacol. 2017 Dec;56:29-34. doi: 10.1016/j.etap.2017.08.030. Epub 2017 Sep 1.
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.
多溴二苯醚（PBDEs）是环境污染物，与2型糖尿病的发生有关，然而，确切机制尚不清楚。特别是，它们对胰岛素分泌的直接影响尚不清楚。在本研究中，我们发现两种多溴二苯醚同系物，即BDE - 47和BDE - 85，可增强INS - 1 832/13细胞中葡萄糖刺激的胰岛素分泌（GSIS）。BDE - 47和BDE - 85对GSIS的这种作用依赖于甲状腺受体（TR）。在急性暴露期间，BDE - 47和BDE - 85（10μM）均激活了Akt。BDE - 47和BDE - 85对Akt的激活在它们对GSIS的增强作用中发挥作用，因为Akt的上游激活剂PI3K的药理学抑制作用与单独使用化合物相比，显著降低了GSIS。本研究表明，BDE - 47和BDE - 85直接作用于胰腺β细胞以刺激GSIS，并且这种作用是由甲状腺受体（TR）和Akt激活介导的。
