A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides

Toxicology. 2014 Aug 1;322:1-13. doi: 10.1016/j.tox.2014.04.009. Epub 2014 May 5.

Abstract

There is increasing evidence reporting that organophosphorus pesticides (OPs) impair glucose homeostasis and cause insulin resistance and type 2 diabetes. Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Formation of advanced glycation end products, accumulation of lipid metabolites, activation of inflammatory pathways and oxidative stress have all been implicated in the pathogenesis of insulin resistance. Ultimately, these molecular processes activate a series of stress pathways involving a family of serine kinases, which in turn have a negative effect on insulin signaling. Experimental and clinical data suggest an association between these molecular mechanisms and OPs compounds. It was first reported that OPs induce hyperglycemia. Then a concomitant increase of blood glucose and insulin was pointed out. For some years only, we have begun to understand that OPs promote insulin resistance and increase the risk of type 2 diabetes. Overall, this review outlines various mechanisms that lead to the development of insulin resistance by OPs exposure.

Keywords: Glucotoxicity; Inflammation; Insulin resistance; Lipotoxicity; Organophosphorus; Oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Glucose / metabolism
  • Glucose / physiology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Insulin Resistance / genetics*
  • Insulin Resistance / physiology*
  • Lipid Metabolism / drug effects
  • Obesity / genetics
  • Obesity / physiopathology
  • Organophosphorus Compounds / toxicity*
  • Oxidative Stress / drug effects
  • Pesticides / toxicity*
  • Signal Transduction / drug effects

Substances

  • Organophosphorus Compounds
  • Pesticides
  • Glucose