Endocrine disruptors in the etiology of type 2 diabetes mellitus

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.