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Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity?

Publication ,  Journal Article
Slotkin, TA
Published in: Reprod Toxicol
April 2011

Human exposures to organophosphate insecticides are ubiquitous. Although regarded as neurotoxicants, increasing evidence points toward lasting metabolic disruption from early-life organophosphate exposures. We gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyclase/cyclic AMP signaling, culminating in hyperresponsiveness to gluconeogenic stimuli. Consequently, the animals developed metabolic dysfunction resembling prediabetes. When the organophosphate-exposed animals consumed a high fat diet in adulthood, metabolic defects were exacerbated and animals gained excess weight compared to unexposed rats on the same diet. At the same time, the high fat diet ameliorated many of the central synaptic defects caused by organophosphate exposure, pointing to nonpharmacologic therapeutic interventions to offset neurodevelopmental abnormalities, as well as toward fostering dietary choices favoring high fat intake. These studies show how common insecticides may contribute to the increased worldwide incidence of obesity and diabetes.

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Published In

Reprod Toxicol

DOI

EISSN

1873-1708

Publication Date

April 2011

Volume

31

Issue

3

Start / End Page

297 / 301

Location

United States

Related Subject Headings

  • Toxicology
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Prediabetic State
  • Organophosphates
  • Obesity
  • Liver
  • Insecticides
  • Humans
 

Citation

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Slotkin, T. A. (2011). Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? Reprod Toxicol, 31(3), 297–301. https://doi.org/10.1016/j.reprotox.2010.07.012
Slotkin, Theodore A. “Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity?Reprod Toxicol 31, no. 3 (April 2011): 297–301. https://doi.org/10.1016/j.reprotox.2010.07.012.
Slotkin, Theodore A. “Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity?Reprod Toxicol, vol. 31, no. 3, Apr. 2011, pp. 297–301. Pubmed, doi:10.1016/j.reprotox.2010.07.012.
Journal cover image

Published In

Reprod Toxicol

DOI

EISSN

1873-1708

Publication Date

April 2011

Volume

31

Issue

3

Start / End Page

297 / 301

Location

United States

Related Subject Headings

  • Toxicology
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Prediabetic State
  • Organophosphates
  • Obesity
  • Liver
  • Insecticides
  • Humans