Dose-dependent effect of Bisphenol-A on insulin signaling molecules in cardiac muscle of adult male rat

Chem Biol Interact. 2017 Mar 25;266:10-16. doi: 10.1016/j.cbi.2017.01.022. Epub 2017 Jan 30.


Environmental contaminant, Bisphenol-A (BPA) is a xenoestrogen, an essential component used for the production of two classes of polymers such as polycarbonate and epoxy resin which disrupts the normal endocrine function. BPA has intense effects on mice endocrine pancreas, an essential tissue involved in glucose metabolism. It disrupts pancreatic β-cell insulin content, induces hyperinsulinemia and insulin resistance in male rats. Cardiac muscle is an insulin responsive organ and insulin has direct effects on glucose transport. The present study was designed to assess the effect of BPA on insulin signaling molecules in the cardiac muscle of adult male Wistar rat. Adult male Wistar rats (200-250 g) were selected and divided into following groups: Group 1: Control (vehicle treated), Group 2: Rats treated with 10 mg BPA/kg b.wt./day for 30 days orally, Group 3: Rats treated with 100 mg BPA/kg b.wt./day for 30 days orally, Group 4: Rats treated with 400 mg BPA/kg b.wt./day for 30 days orally. IR (insulin receptor) and pIRTyr1162 proteins were significantly decreased in the high dose group (400 mg). There was no change in IRS1 (insulin receptor substrate-1) and Akt proteins. Whereas, a decrease in pIRS1Tyr632 (100 mg and 400 mg), pAkt Ser473 (400 mg) and GLUT4 (glucose transporter 4) (cytosolic and plasma membrane) proteins was observed which may affect the cardiovascular function. It is concluded that BPA exposure has adverse effect on cardiac insulin signal transduction which may affect its function.

Keywords: Bisphenol-A; Cardiac muscle; Diabetes; Endocrine disruptor; Insulin resistance; Insulin signaling molecules.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Blood Glucose / metabolism
  • Dose-Response Relationship, Drug
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism*
  • Male
  • Myocardium / metabolism*
  • Phenols / pharmacology*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*


  • Benzhydryl Compounds
  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Phenols
  • Slc2a4 protein, rat
  • bisphenol A