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Paloma Alonso-Magdalena,¹ Sumiko Morimoto,^1,2 Cristina Ripoll,¹ Esther Fuentes,¹ and Angel Nadal¹

¹Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Alicante, Spain; ²Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," México City, México

Abstract
The function of the pancreatic β-cell is the storage and release of insulin, the main hormone involved in blood glucose homeostasis. The results in this article show that the widespread environmental contaminant bisphenol-A (BPA) imitates 17β-estradiol (E₂) effects in vivo on blood glucose homeostasis through genomic and nongenomic pathways. The exposure of adult mice to a single low dose (10 µg/kg) of either E₂ or BPA induces a rapid decrease in glycemia that correlates with a rise of plasma insulin. Longer exposures to E₂ and BPA induce an increase in pancreatic β-cell insulin content in an estrogen-receptor-dependent manner. This effect is visible after 2 days of treatment and starting at doses as low as 10 µg/kg/day. After 4 days of treatment with either E₂ or BPA, these mice developed chronic hyperinsulinemia, and their glucose and insulin tolerance tests were altered. These experiments unveil the link between environmental estrogens and insulin resistance. Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia. Key words: bisphenol A, diabetes, endocrine disruptors, estradiol, estrogen receptor, insulin, islet of Langerhans, nongenomic, xenoestrogens. Environ Health Perspect 114:106-112 (2006) . doi:10.1289/ehp.8451 available via http://dx.doi.org/ [Online 20 September 2005]

Address correspondence to A. Nadal, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Carretera Alicante-Valencia Km 87, Sant Joan d'Alacant, 03550 Alicante, Spain. Telephone: 34-96-5919535. Fax: 34-96-5919547. E-mail: nadal@umh.es

We thank B. Fernández for excellent technical assistance and I. Quesada, A. Gomis, and A.B. Ropero for critical reading of the manuscript.

This study was supported by the Spanish Ministry of Education and Science (grant BFI2002-01469 and BFU2005-01052) and Instituto de Salud Carlos III (grants RCMN C03/08 and 03/0178) . P.A.M. has a fellowship from the Ministry of Education and Science. S.M. was a postdoctoral fellow from CONACYT, Mexico.

The authors declare they have no competing financial interests.

Received 30 June 2005 ; accepted 19 September 2005.