title: 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.affiliation: Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Wuhan, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wei
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.forename: Shunqing
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2; D004785:Environmental Pollutants / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors
chemical_list: D004785:Environmental Pollutants; D004967:Estrogens; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen