Low-level phenolic estrogen pollutants impair islet morphology and β-cell function in isolated rat islets.

Abstract

Phenolic estrogen pollutants, a class of typical endocrine-disrupting chemicals, have attracted public attention due to their estrogenic activities of imitating steroid hormone 17β-estradiol (E(2)) effects. Exposure to these pollutants may disrupt insulin secretion and be a risk factor for type 2 diabetes. In this study, we investigated the direct effects of phenolic estrogen diethylstilbestrol (DES), octylphenol (OP), nonylphenol (NP), and bisphenol A (BPA) on rat pancreatic islets in vitro, whose estrogenic activities were DES>NP>OP>BPA. Isolated β-cells were exposed to E(2), DES, OP, NP, or BPA (0, 0.1, 0.5, 2.5, 25, and 250 μg/l) for 24 h. Parameters of insulin secretion, content, and morphology of β-cells were measured. In the glucose-stimulated insulin secretion test, E(2) and DES increased insulin secretion in a dose-dependent manner in a 16.7 mM glucose condition. However, for BPA, NP, or OP with lower estrogenic activity, the relationship between the doses and insulin secretion was an inverted U-shape. Moreover, OP, NP, or BPA (25 μg/l) impaired mitochondrial function in β-cells and induced remarkable swelling of mitochondria with loss of distinct cristae structure within the membrane, which was accompanied by disruption of mRNA expression of genes playing a key role in β-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1α, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). Therefore, these phenolic estrogens can disrupt islet morphology and β-cell function, and mitochondrial dysfunction is suggested to play an important role in the impairment of β-cell function.

• Authors: Liqiong Song, Wei Xia, Zhao Zhou, Yuanyuan Li, Yi Lin, Jie Wei, Zhengzheng Wei, Bing Xu, Jie Shen, Weiyong Li, Shunqing Xu
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 215 Issue 2 Pg. 303-11 (Nov 2012) ISSN: 1479-6805 [Electronic] England
• PMID: 22946080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Environmental Pollutants
• Estrogens
• Phenols
• RNA, Messenger
• Receptors, Estrogen

Topics

• Animals
• Diabetes Mellitus, Type 2
• Environmental Pollutants (toxicity)
• Estrogens (toxicity)
• Islets of Langerhans (drug effects)
• Male
• Mitochondria (metabolism)
• Phenols (toxicity)
• Protein Array Analysis
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Estrogen (metabolism)
• Risk Factors