Effect of Bisphenol-A (BPA) on insulin signal transduction and GLUT4 translocation in gastrocnemius muscle of adult male albino rat

Int J Biochem Cell Biol. 2017 Sep;90:38-47. doi: 10.1016/j.biocel.2017.07.015. Epub 2017 Jul 21.

Abstract

Environmental estrogens bind to estrogen receptors, mimic estrogenic actions, and have adverse effects on human health like Bisphenol - A (BPA) which is used as a monomer in the production of polycarbonate plastics (PC) and epoxy resins which are used in variety of canned foods. Skeletal muscle plays an essential role in maintaining systemic glucose metabolism. In the present study, we investigated the possible effects of BPA on insulin signalling molecules and GLUT4 translocation in the gastrocnemius muscle of adult male rat. Rats were divided into four groups - Group I: Control (vehicle-corn oil treated), Group II, III and IV were administered with BPA (10, 100 and 400mg/kg b.wt/day, respectively) through oral gavage. Fasting blood glucose level of BPA treated groups showed a significant increase, oral glucose tolerance and insulin tolerance were also impaired in these animals. BPA significantly decreased the protein levels of insulin signalling molecules like IR, IRS-1, Akt, AS160 and its phosphorylated forms and blunts GLUT4 translocation by altering the levels of v- and t- SNARE proteins that assist the translocation process, thereby decreasing glucose uptake and oxidation in the gastrocnemius muscle. These results suggest that BPA has detrimental effects on insulin signalling molecules and GLUT4 translocation in the gastrocnemius muscle and thus impairs glucose homeostasis.

Keywords: BPA; Endocrine disruptor; GLUT4 translocation; Insulin resistance; Insulin signalling molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Endocrine Disruptors / pharmacology*
  • Glucose Transporter Type 4 / metabolism*
  • Hormones / blood
  • Insulin / metabolism*
  • Male
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phenols / pharmacology*
  • Protein Transport / drug effects
  • Rats
  • Signal Transduction / drug effects*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Glucose Transporter Type 4
  • Hormones
  • Insulin
  • Phenols
  • bisphenol A