Endocrine Abstracts

Diabetes prevalence has been worryingly growing in recent decades, reaching pandemic proportions. Genetic and environmental factors play a role in diabetes aetiology. While the genetic background may predispose individuals to the disease, environmental factors, including exposure to chemical pollutants that can disrupt metabolic functions (also known as metabolism disrupting chemicals or MDCs), may act as triggers to diabetes development. Despite growing evidence suggesting a relationship between exposure to MDCs and diabetes susceptibility, there is a lack of test protocols that allow the identification of MDCs with diabetogenic activity. According to the European regulation of chemicals, information on a chemical’s endocrine mode of action and related adverse effects relevant for human health are required as criteria to identify MDCs. Nevertheless, there are no suitable in vitro tests for regulatory purposes that identify the potential metabolism disrupting effects of compounds. In GOLIATH, a project within the Horizon 2020 programme of the European Commission seeking to address the urgent need to develop test protocols that allow the identification of MDCs, one of our aims is to design test methods that identify MDCs that could affect β-cells. For this purpose, we used human and rat β-cell lines as well as dispersed mouse islet cells as in vitro models. We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM): Bisphenol-A, tributyltin, perfluorooctanoic acid, triphenylphosphate, triclosan, and dichlorodiphenyldichloroethylene. To test these chemicals, we followed an adverse outcome pathway framework, where we studied the molecular initiated event and key events, including gene expression and reactive oxygen species production. Finally, we evaluated viability and glucose-stimulated insulin secretion as adverse effects. We propose that the optimization of the test methods detailed in our study could be incorporated into a set of protocols for the identification of MDCS.