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Endocrine disruptors in the etiology of type 2 diabetes mellitus

Nature Reviews Endocrinology volume 7, pages 346–353 (2011)Cite this article

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Abstract

The etiology of type 2 diabetes mellitus involves the induction of insulin resistance along with the disruption of pancreatic β-cell function and the loss of β-cell mass. In addition to a genetic predisposition, lifestyle factors seem to have an important role. Epidemiological studies indicate that the increased presence of endocrine disrupting chemicals (EDCs) in the environment may also play an important part in the incidence of metabolic diseases. Widespread EDCs, such as dioxins, pesticides and bisphenol A, cause insulin resistance and alter β-cell function in animal models. These EDCs are present in human blood and can accumulate in and be released from adipocytes. After binding to cellular receptors and other targets, EDCs either imitate or block hormonal responses. Many of them act as estrogens in insulin-sensitive tissues and in β cells, generating a pregnancy-like metabolic state characterized by insulin resistance and hyperinsulinemia. Adult exposure in mice produces insulin resistance and other metabolic alterations; in addition, during pregnancy, EDCs alter glucose metabolism in female mice, as well as glucose homeostasis and endocrine pancreatic function in offspring. Although more experimental work is necessary, evidence already exists to consider exposure to EDCs as a risk factor in the etiology of type 2 diabetes mellitus and other diseases related to insulin resistance.

Key Points

  • The prevalence of type 2 diabetes mellitus (T2DM) has increased dramatically worldwide, making the disease one of the fastest growing public health problems

  • The etiology of T2DM is based on the induction of insulin resistance together with functional disruption of insulin producing β cells; genetic predisposition and environmental factors play key roles

  • Some widespread endocrine disrupting chemicals (EDCs), at concentrations found in human plasma, induce insulin resistance and alter pancreatic β-cell function in cellular and adult animal models

  • Epidemiological data indicate that exposure to EDCs is linked to an increased risk of diabetes mellitus in adults

  • Data obtained from pregnant mice and offspring indicate that short exposure to the EDC bisphenol A during pregnancy disrupts glucose homeostasis in female mice and their adult male offspring

  • Sufficient scientific evidence is available to consider the exposure to persistent organic pollutants, including bisphenol A, a risk factor for T2DM and other metabolic disorders

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Figure 1: Pregnancy-like actions of endocrine disrupting chemicals on islet function and glucose homeostasis.

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Acknowledgements

The authors laboratories are funded by “Ministerio de Ciencia e Innovación” and “Generalitat Valenciana”. CIBERDEM is an initiative of “Instituto de Salud Carlos III”. The authors thank Elaine Vieira, Sergi Soriano, Laura Marroquí and Esther Fuentes for critical reading of the manuscript. We thank the members of our laboratories for their continuous input and discussion.

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  1. Institute of Bioengineering and CIBERDEM, Miguel Hernandez University, Edifício Vinalopó, Avenida de la Universidad s/n 03202 Elche, Alicante, Spain

    Paloma Alonso-Magdalena, Ivan Quesada & Angel Nadal

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  1. Paloma Alonso-Magdalena
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P. Alonso-Magdalena and A. Nadal contributed to researching data for the article, all authors provided a substantial contribution to the discussion of content, A. Nadal wrote the article and all authors reviewed/edited the manuscript before submission.

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Correspondence to Angel Nadal.

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Alonso-Magdalena, P., Quesada, I. & Nadal, A. Endocrine disruptors in the etiology of type 2 diabetes mellitus. Nat Rev Endocrinol 7, 346–353 (2011). https://doi.org/10.1038/nrendo.2011.56

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