Mitochondria as target of endocrine-disrupting chemicals: implications for type 2 diabetes

J Endocrinol. 2018 Nov 1;239(2):R27-R45. doi: 10.1530/JOE-18-0362.

Abstract

Type 2 diabetes is a chronic, heterogeneous syndrome characterized by insulin resistance and pancreatic β-cell dysfunction or death. Among several environmental factors contributing to type 2 diabetes development, endocrine-disrupting chemicals (EDCs) have been receiving special attention. These chemicals include a wide variety of pollutants, from components of plastic to pesticides, with the ability to modulate endocrine system function. EDCs can affect multiple cellular processes, including some related to energy production and utilization, leading to alterations in energy homeostasis. Mitochondria are primarily implicated in cellular energy conversion, although they also participate in other processes, such as hormone secretion and apoptosis. In fact, mitochondrial dysfunction due to reduced oxidative capacity, impaired lipid oxidation and increased oxidative stress has been linked to insulin resistance and type 2 diabetes. Herein, we review the main mechanisms whereby metabolism-disrupting chemical (MDC), a subclass of EDCs that disturbs energy homeostasis, cause mitochondrial dysfunction, thus contributing to the establishment of insulin resistance and type 2 diabetes. We conclude that MDC-induced mitochondrial dysfunction, which is mainly characterized by perturbations in mitochondrial bioenergetics, biogenesis and dynamics, excessive reactive oxygen species production and activation of the mitochondrial pathway of apoptosis, seems to be a relevant mechanism linking MDCs to type 2 diabetes development.

Keywords: endocrine-disrupting chemicals; insulin resistance; metabolism-disrupting chemical; mitochondria; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Endocrine Disruptors / toxicity*
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Dynamics / drug effects

Substances

  • Endocrine Disruptors