The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function
            <i>In Vivo</i>
            and Induces Insulin Resistance

Alonso-Magdalena, Paloma; Morimoto, Sumiko; Ripoll, Cristina; Fuentes, Esther; Nadal, Ángel

doi:10.1289/ehp.8451

Cited by 552 publications

(431 citation statements)

References 55 publications

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“…Therefore, it is reasonable to suggest that BPA, similarly to E2, binds to ERa and produces changes in these rapid signals. Few data address the ability of BPA to mediate nongenomic estrogenic actions (see [25][26][27][28][29][30][31] and, as far we know, no information focuses on the involvement of these pathways in the proliferative effect of BPA.…”

Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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SummaryA wide variety of environmental contaminants exert estrogenic actions in wildlife, laboratory animals, and in human beings through binding to nuclear estrogen receptors (ERs). Here, the mechanism(s) of bisphenol A (BPA) to induce cell proliferation and the occurrence of its bioremediation by treatment with laccase are reported. BPA, highly present in natural world and considered as a model of environmental estrogen action complexity, promotes human cancer cell proliferation via ERa-dependent signal transduction pathways. Similar to 17b-estradiol, BPA increases the phosphorylation of both extracellular regulated kinase and AKT. Specific inhibitors of these kinase completely block the BPA effect on cancer cell proliferation. Notably, high BPA concentrations (i.e., 0.1 and 1 mM) are cytotoxic even in ERa-devoid cancer cells, indicating that an ERa-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERa loosing at all ERa-dependent effect on cancer cell proliferation. Moreover, the laccase-catalyzed oxidation of BPA reduces the BPA cytotoxic effect. Thus, laccase appears to impair BPA action(s), representing an invaluable bioremediation enzyme.2008 IUBMB IUBMB Life, 60(12): 843-852, 2008

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Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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“…Physiological levels of estrogen are involved in maintaining normal insulin sensitivity, but an excess of estrogen, such as exposure to chemicals with estrogenic activity at an inappropriate concentration, would increase the risk of developing insulin resistance and diabetes (Zhang et al 2002, Margolis et al 2004, Godsland 2005. One of the most striking examples is that adult male mice injected with a daily dose of 100 mg/kg per day bisphenol A (BPA) or 17b-estradiol (E 2 ) for 4 days showed higher insulin secretion, thereby resulting in insulin resistance and postprandial hyperinsulinemia (Alonso-Magdalena et al 2006). Our previous studies also have demonstrated that perinatal exposure to 50 mg/kg per day BPA led to severe glucose and insulin intolerance in adult rat offspring along with progressive damage of b-cells .…”

Section: Introductionmentioning

confidence: 99%

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

Song¹,

Xia²,

Zhao³

et al. 2012

Journal of Endocrinology

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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.

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“…The potencies of these compounds in nuclear transcription reporter assays range from very weak (dieldrin, DDE, endosulfan), to somewhat weak (bisphenol A and nonylphenol), to quite strong (DES and coumestrol). There is a paucity of data on the ability of environmental estrogens to mediate nongenomic effects at low concentrations [18][19][20][21][22][23][24]. Most published studies examine only very high (μM-mM) concentrations (for example, [25]) in the range required to see any effects on nuclear transcription responses, but which are rarely reached at contamination sites.…”

Section: Introduction Xenoestrogens and Their Known Modes Of Actionmentioning

confidence: 99%

Xenoestrogens are potent activators of nongenomic estrogenic responses

et al. 2007

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Studies of the nuclear transcriptional regulatory activities of nonphysiological estrogens have not explained their actions in mediating endocrine disruption in animals and humans at the low concentrations widespread in the environment. However, xenoestrogens have rarely been tested for their ability to participate in the plethora of nongenomic steroid signaling pathways elucidated over the last several years. Here we review what is known about such responses in comparison to our recent evidence that xenoestrogens can rapidly and potently elicit signaling through nongenomic pathways culminating in functional endpoints. Both estradiol (E 2 ) and compounds representing various classes of xenoestrogens (diethylstilbestrol, coumestrol, bisphenol A, DDE, nonylphenol, endosulfan, and dieldrin) act via a membrane version of the estrogen receptor-α on pituitary cells, and can provoke Ca ++ influx via L-type channels, leading to prolactin (PRL) secretion. These hormones and mimetics can also cause the oscillating activation of extracellular regulated kinases (ERKs). However, individual estrogen mimetics differ in their potency and temporal phasing of these activations compared to each other and to E 2 . It is perhaps in these ways that they disrupt some endocrine functions when acting in combination with physiological estrogens. Our quantitative assays allow comparison of these outcomes for each mimetic, and let us build a detailed picture of alternative signaling pathway usage. Such an understanding should allow us to determine the estrogenic or antiestrogenic potential of different types of xenoestrogens, and help us to develop strategies for preventing xenoestrogenic disruption of estrogen action in many tissues.

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The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance

Cited by 552 publications

References 55 publications

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

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

Xenoestrogens are potent activators of nongenomic estrogenic responses

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