Long-term bisphenol A exposure accelerates insulitis development in diabetes-prone NOD mice

Immunopharmacol Immunotoxicol. 2013 Jun;35(3):349-58. doi: 10.3109/08923973.2013.772195. Epub 2013 Mar 18.

Abstract

Exposure to the endocrine disruptor (ED) bisphenol A (BPA) used in polycarbonate plastic and epoxy resins appears ubiquitous since BPA can be found in over 90% of analyzed urine samples from all age groups. There is a parallel occurrence of increased prevalence in type 1 diabetes mellitus (T1DM) and an increased exposure to EDs the last decades. T1DM is caused by insulin deficiency due to autoimmune destruction of insulin producing pancreatic beta cells and has been suggested to be induced by various environmental factors acting together with a genetic predisposition. The objective of the present study was to investigate the effect of BPA (0, 1 and 100 mg/l BPA in the drinking water) on T1DM development in nonobese diabetic (NOD) mice, spontaneously developing T1DM. Histological evaluation of pancreas from 12-weeks-old female mice revealed significantly increased insulitis in mice exposed to 1 mg/l BPA, while the insulitis was less severe at the higher BPA exposure. Serum glucose levels in the 1 mg/ml BPA group tended to be hyperglycaemic, also indicating an accelerated onset of T1DM. The high BPA exposure seemed to counteract the diabetes development in females and also in male NOD mice for both BPA concentrations. Prior to insulitis, both BPA concentrations resulted in increased apoptosis and reduced numbers of tissue resident macrophages in pancreatic islets. In conclusion, long-term BPA exposure at a dose three times higher than the tolerable daily intake of 50 µg/kg, appeared to accelerate spontaneous insulitis and diabetes development in NOD mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autoantibodies / blood
  • Benzhydryl Compounds / toxicity*
  • Blood Glucose / analysis
  • Cytokines / blood
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / chemically induced*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease*
  • Insulin / immunology
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Mice
  • Mice, Inbred NOD
  • Pancreas / drug effects*
  • Pancreas / immunology
  • Pancreas / metabolism
  • Pancreas / pathology
  • Phenols / toxicity*

Substances

  • Autoantibodies
  • Benzhydryl Compounds
  • Blood Glucose
  • Cytokines
  • Endocrine Disruptors
  • Insulin
  • Phenols
  • bisphenol A