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

Phenolic estrogen pollutants, a class of typical endocrine-disrupting chemicals, have attracted public attention due to their estrogenic activities of imitating steroid hormone 17 beta-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 beta-cells were exposed to E-2, DES, OP, NP, or BPA (0, 0.1, 0.5, 2.5, 25, and 250 mu g/l) for 24 h. Parameters of insulin secretion, content, and morphology of beta-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 mu g/l) impaired mitochondrial function in beta-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 beta-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1 alpha, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). Therefore, these phenolic estrogens can disrupt islet morphology and beta-cell function, and mitochondrial dysfunction is suggested to play an important role in the impairment of beta-cell function. Journal of Endocrinology (2012) 215, 303-311