Transient Gestational Exposure to Drinking Water Containing Excess Hexavalent Chromium Modifies Insulin Signaling in Liver and Skeletal Muscle of Rat Progeny

Chem Biol Interact. 2017 Nov 1;277:119-128. doi: 10.1016/j.cbi.2017.09.003. Epub 2017 Sep 11.

Abstract

Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure. We tested the hypothesis "transient gestational exposure to drinking water containing excess CrVI may modify insulin signaling during postnatal life". Pregnant Wistar rats were given drinking water containing 50, 100 and 200 ppm CrVI (K2Cr2O7) from gestational day 9-14 encompassing the period of organogenesis; the male progenies were tested at postnatal day 60. Neither fasting blood glucose nor oral glucose tolerance was altered in CrVI treated progeny. Nevertheless, western blot detection pointed out attenuated expression level of insulin receptor (IR), its downstream signaling molecules (IRS-1, pIRS-1Tyr632, Akt and pAktSer473) and organ specific glucose transporters (GLUT2 in liver and GLUT4 in gastrocnemius muscle), along with a significant increase in serum insulin level in male progenies exposed to CrVI. While 14C-2-deoxy glucose uptake increased in the liver, the same decreased in the skeletal muscle whereas, 14C-glucose oxidation recorded a consistent decrease in both tissues of CrVI exposed rats. These findings support our hypothesis and suggest that transient gestational exposure to excess CrVI may affect insulin signaling and glucose oxidation in the progeny, predictably rendering them vulnerable to insulin resistance.

Keywords: Chromium toxicity; Glucose homeostasis; Glucose transporters; Insulin receptor.

MeSH terms

  • Animals
  • Chromium / analysis
  • Chromium / toxicity*
  • Drinking Water / adverse effects*
  • Drinking Water / chemistry
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 2 / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism*
  • Insulin Resistance
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Maternal Exposure / adverse effects*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Water Pollutants, Chemical / analysis
  • Water Pollutants, Chemical / toxicity*

Substances

  • Drinking Water
  • Glucose Transporter Type 2
  • Glucose Transporter Type 4
  • Insulin
  • Water Pollutants, Chemical
  • Chromium
  • chromium hexavalent ion
  • Glucose