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Environ Pollut. 2019 Jun;249:822-830. doi: 10.1016/j.envpol.2019.03.101. Epub 2019 Mar 27.

Exposure to Aroclor 1254 persistently suppresses the functions of pancreatic β-cells and deteriorates glucose homeostasis in male mice.

Author information

1
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China.
2
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China. Electronic address: cgwang@xmu.edu.cn.

Abstract

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been shown to be related to the occurrence of type 2 diabetes mellitus (T2DM). Nevertheless, it is necessary to further explore the development of T2DM caused by PCBs and its underlying mechanisms. In the present study, 21-day-old C57BL/6 male mice were orally treated with Aroclor 1254 (0.5, 5, 50 or 500 μg kg-1) once every three days. After exposure for 66 d, the mice showed impaired glucose tolerance, 13% and 14% increased fasting serum insulin levels (FSIL), and 63% and 69% increases of the pancreatic β-cell mass in the 50 and 500 μg kg-1 groups, respectively. After stopping exposure for 90 d, treated mice returned to normoglycemia and normal FSIL. After re-exposure of these recovered mice to Aroclor 1254 for 30 d, fasting plasma glucose showed 15%, 28% and 16% increase in the 5, 50 and 500 μg kg-1 treatments, FSIL exhibited 35%, 27%, 30% and 32% decrease in the 0.5, 5, 50 or 500 μg kg-1 groups respectively, and there was no change in pancreatic β-cell mass. Transcription of the pancreatic insulin gene (Ins2) was significantly down-regulated in the 50 and 500 μg kg-1 groups, while DNA-methylation levels were simultaneously increased in the Ins2 promoter during the course of exposure, recovery and re-exposure. Reduced insulin levels were initially rescued by a compensative increase in β-cell mass. However, β-cell mass eventually failed to make sufficient levels of insulin, resulting in significant increases in fasting blood glucose, and indicating the development of T2DM.

KEYWORDS:

Dynamic effects; Epigenetic; Glucose homeostasis; Insulin level; Polychlorinated biphenyls

PMID:
30953944
DOI:
10.1016/j.envpol.2019.03.101
[Indexed for MEDLINE]

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