Influence of Bisphenol A on Type 2 Diabetes Mellitus

Abstract

Bisphenol A (BPA) is an organic synthetic compound employed to produce plastics and epoxy resins. It is used as a structural component in polycarbonate beverage bottles and as coating for metal surface in food containers and packaging. The adverse effects of BPA on human health are widely disputed. BPA has been recently associated with a wide variety of medical disorders and, in particular, it was identified as potential endocrine-disrupting compound with diabetogenic action. Most of the clinical observational studies in humans reveal a positive link between BPA exposure, evaluated by the measurement of urinary BPA levels, and the risk of developing type 2 diabetes mellitus. Clinical studies on humans and preclinical studies on in vivo, ex vivo, and in vitro models indicate that BPA, mostly at low doses, may have a role in increasing type 2 diabetes mellitus developmental risk, directly acting on pancreatic cells, in which BPA induces the impairment of insulin and glucagon secretion, triggers inhibition of cell growth and apoptosis, and acts on muscle, hepatic, and adipose cell function, triggering an insulin-resistant state. The current review summarizes the available evidences regarding the association between BPA and type 2 diabetes mellitus, focusing on both clinical and preclinical studies.

Bisphenol A: an emerging threat to female fertility

“…The estimated daily intake for adults is around 1.5 μg/kg bw/day. Moreover, WHO, Food and Drug Administration (FDA) and European Food Safety Authority (EFSA), based on rodent studies, have also determined the no adverse effect level (NOAEL) for the systemic toxicity of BPA in animals, corresponding, for dietary exposure, to 5 mg/kg bw/day [13,47]. In consideration of the differences in toxicokinetics among the species, EFSA, on grounds of prudence, applied a default uncertainty factor of 100 to the overall NOAEL and of 1000 to the overall LOAEL, establishing a TDI of 0.05 mg/kg bw (50 μg/kg bw/day) for humans over the life-time [13].…”

“…BPA is metabolized and inactivated through glucuronidation by uridine diphosphate glucuronosyltransferases and sulfation, by phenolsulfotransferases in hepatocytes microsomes. The conjugated, glucuronidated and sulfated, inactive forms of BPA acquire hydrophilic characteristics and are excreted into the bile and urine, with a half-life corresponding to around 6 hours [47][48][49]. Nevertheless, the expression of β-glucuronidase enzyme, a member of the glycosidase family of enzymes which cleave the glucuronide group from the metabolite via hydrolysis, in several tissues, like lungs, liver, kidneys and placenta of animals and humans, ensures deconjugation of BPA and therefore the release of its active form into the blood and again its distribution into the body [50].…”

Detection of bisphenol A and derivatives in human urineviacyclodextrin-promoted fluorescence modulation

“…Among the list of known and suspected environmental toxicants, bisphenol A (BPA) and its derivatives, 1 including bisphenol S (BPS) and bisphenol F (BPF), 2 have received a significant amount of attention in both the scientific literature 3 and the popular media. BPA is a suspected endocrine disruptor, 4 and exposure to BPA and associated derivatives is correlated with increased rates of asthma, 5 inflammatory bowel disease, 6 endocrine disorders, 7 and certain cancer sub-types. 8 These negative health effects are particularly concerning because of BPA's ubiquitous presence in a variety of commercial products, including plastic water bottles 9 and bags, 10 liners of canned food products, 11 infant bottles 12 and training (i.e.…”

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

“…Significant exposure often occurs by consuming food and beverages contaminated with BPA and in dental procedures, so that up to 92.6% of the human population has detectable BPA levels in their bodies 3,4 . Epidemiological studies have demonstrated that higher BPA urine concentrations are associated with increased morbidity and mortality from cardiovascular diseases 5,6 , and several studies in humans and animal models have suggested a causative role for BPA in cardiovascular disease including hypertension, atherosclerosis, cardiac hypertrophy and arrythmias [7][8][9][10] . Recently, it has been reported that a life long exposure to BPA in rodents produces arrhythmogenic effects 11 .…”