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

• Published in: Molecular and cellular biochemistry Vol. 458; no. 1-2; pp. 171 - 183
• Main Authors: Soundararajan, Avinash, Prabu, Paramasivam, Mohan, Viswanathan, Gibert, Yann, Balasubramanyam, Muthuswamy
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019; Springer; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Bisphenol A; Cardiology; Cardiovascular diseases; Care and treatment; Comparative analysis; Correlation analysis; Development and progression; Dextrose; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes therapy; Endocrine disruptors; Enzyme-linked immunosorbent assay; Epoxy resins; Estrogen; Estrogen receptors; Estrogens; Ethylenediaminetetraacetic acid; Etiology; Gene expression; Glucose; Glucose tolerance; Heart diseases; Inflammation; Insulin; Insulin resistance; Interleukin 6; Leukocytes (mononuclear); Life Sciences; Markers; Medical Biochemistry; Oncology; Organic chemistry; p53 Protein; Patients; Peripheral blood mononuclear cells; Receptors; Risk factors; RNA; Senescence; Serum levels; Telomeres; Tumor necrosis factor-α; Tumor proteins; Type 2 diabetes; T2DM; Insulin resistance; Senescence; Inflammation; Bisphenol-A; ERRγ
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-019-03540-9

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. Graphical abstract