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Novel insights of elevated systemic levels of bisphenol-A (BPA) linked to poor glycemic control, accelerated cellular senescence and insulin resistance in patients with type 2 diabetes

journal contribution
posted on 2019-08-01, 00:00 authored by Avinash Soundararajan, Paramasivam Prabu, Viswanathan Mohan, Yann Gibert, Muthuswamy Balasubramanyam
There is a striking interaction of genes and environment in the etiology of type 2 diabetes mellitus (T2DM). While endocrine disrupting chemicals (EDCs) like bisphenol-A (BPA) have received special attention for their mechanistic role in metabolic disruption, there is a lack of clinically relevant data on BPA levels in Asian Indians, a population which is more susceptible to type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Therefore, we measured systemic levels of BPA in patients with T2DM compared to individuals with normal glucose tolerance (n = 30 each). Serum BPA levels were estimated using ELISA kit, and biochemical determinations were done by standard protocols. Peripheral blood mononuclear cells (PBMCs) were used to profile the gene expression alterations with special reference to inflammation, estrogen receptors, and cellular senescence in these subjects. Serum levels of BPA were significantly higher in patients with T2DM compared to control individuals and positively correlated to poor glycemic control and insulin resistance. Patients with T2DM exhibited significantly elevated mRNA levels of senescence (GLB1, p16, p21, and p53) and inflammatory (IL6 and TNF-α) markers, shortened telomeres as well as elevated levels of estrogen-related receptor gamma (ERRγ), a recently identified receptor for BPA. BPA levels were positively correlated to senescence indicators, inflammatory markers and ERRγ and negatively correlated to telomere length. Our study is the first data in the clinical diabetes setting to demonstrate an association of increased BPA levels with cellular senescence, proinflammation, poor glycemic control, insulin resistance, and shortened telomeres in patients with T2DM.

History

Journal

Molecular and cellular biochemistry

Volume

458

Issue

1-2

Pagination

171 - 183

Publisher

Springer

Location

Amsterdam, The Netherlands

eISSN

1573-4919

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2019, Springer Science+Business Media, LLC, part of Springer Nature