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

Abstract

Phenolic estrogen pollutants, a class of typical endocrinedisrupting chemicals, have attracted public attention due to their estrogenic activities of imitating steroid hormone 17b-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 DESONPOOPOBPA. Isolated b-cells were exposed to E 2 , DES, OP, NP, or BPA (0, 0 . 1, 0 . 5, 2 . 5, 25, and 250 mg/l) for 24 h. Parameters of insulin secretion, content, and morphology of b-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 mg/l) impaired mitochondrial function in b-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 b-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1a, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). Therefore, these phenolic estrogens can disrupt islet morphology and b-cell function, and mitochondrial dysfunction is suggested to play an important role in the impairment of b-cell function.

Alteration Effect of Exendin-4 on Oxidative Stress and Metabolic Disorders Induced by Bisphenol A in Adult Male Mice

“…Nowadays phenolic pollutants such as Bisphenol A (BPA) are common endocrine disruptor chemicals (EDCs) that intervene with classic and non-classic receptors of estrogen. Inappropriate activation of estrogen receptors is associated with problems such as type II diabetes and metabolic disorders (2)(3)(4).…”

International Trade Regulations on BPA: Global Health and Economic Implications

“…Hypertension (Bodin et al, 2013; 189.2 382 2. Diabetes (Leranth et al, 2008;Song et al, 2012;Babu et al, 2013;Gong et al, 2013;Kim and Park, 2013 …”

Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting Chemicals

“…The insulin exocytic machinery is similarly disrupted by phenolic compounds, widely used in adhesives and detergents. Exposure to low levels of phenolic estrogens reduced mRNA expression of Snap25 and Rab27a in rodent islets [19]. In contrast, polychlorinated biphenyl (PCB) treatment increased calcium influx and insulin secretion in a calcium/calmodulin-dependent protein kinase II (CaMKII)-dependent fashion [20].…”

“…Mitochondria are critical regulators of the cellular redox balance, responsible for both ROS and antioxidant production; thus perturbations to mitochondrial integrity leads to increased cellular stress. Several MDCs promote oxidative stress in β-cells, including BPA [19,29], arsenic [30,31], and diethylhexylphthalate (DEHP) [32]. For example, rat islets exposed to the phenolic compounds octylphenol, nonylphenol, and BPA exhibited disruptions in islet mitochondrial architecture with alterations in mitochondrial gene expression [19].…”