Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway

Can J Diabetes. 2017 Jun;41(3):273-280. doi: 10.1016/j.jcjd.2016.10.008. Epub 2017 Feb 22.

Abstract

Objectives: Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood.

Methods: Fasting blood sugar and glucose tolerance tests were evaluated.

Results: In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic.

Conclusions: The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant.

Keywords: N-acetylcysteine; N-acétylcystéine; arsenic; carvedilol; carvédilol; diabetes; diabète; espèces réactives de l'oxygène; propranolol; reactive oxygen species.

MeSH terms

  • Acute Disease
  • Adrenergic Agents / pharmacology*
  • Adrenergic Agents / therapeutic use
  • Animals
  • Arsenic / administration & dosage
  • Arsenic / toxicity*
  • Blood Glucose / metabolism
  • Chronic Disease
  • Glucose / metabolism
  • Glucose Intolerance / blood*
  • Glucose Intolerance / chemically induced*
  • Glucose Intolerance / prevention & control
  • Male
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Adrenergic Agents
  • Blood Glucose
  • Reactive Oxygen Species
  • Glucose
  • Arsenic