G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERα and ERβ in pancreatic beta cells

Babiloni-Chust, Ignacio; Santos, Reinaldo Sousa Dos; Medina-Gali, Regla María; Perez-Serna, Atenea Alexandra; Encinar, José-Antonio; Martı́nez-Pinna, Juan; Gustafsson, Jan‐Åke; Marroquí, Laura; Nadal, Ángel

doi:10.1016/j.envint.2022.107250

Cited by 24 publications

(29 citation statements)

References 65 publications

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“…For this purpose, we measured ROS production and the expression of two ER stress markers, namely BiP and p-eIF2α. Like it has been previously reported in β-cells [18][19][20][21][22]38], BPA and TBT induced ROS production in αTC1-9 cells; of note, exposure to the other four MDCs did not change ROS production at the concentrations tested. As ROS levels were increased only by chemicals that induced apoptosis, it is reasonable to state that generation of ROS is a key event in the pathway to MDC-induced α-cell apoptosis.…”

Section: α-Cell Viability Testssupporting

confidence: 81%

“…Cells extracts were resolved on 12% SDS-PAGE and transferred to nitrocellulose membrane (Bio-Rad). Immunoblot analysis was performed by overnight incubation with antibodies against BiP, p-eIF2α, and α-Tubulin as described [19]. The antibodies used herein are listed in Supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoblot analysis was performed by overnight incubation with antibodies against BiP, p-eIF2α, and α-Tubulin as described [19]. The antibodies used herein are listed in Supplementary Table 1.…”

Section: Western Blottingmentioning

confidence: 99%

“…For instance, bisphenol A (BPA), a well-studied MDC, can alter insulin secretion in primary mouse islets/β-cells by activating estrogen receptors and altering ion channel expression and activity [14][15][16][17]. Moreover, BPA induces β-cell apoptosis in an estrogen receptordependent manner, where BPA increases reactive oxygen species (ROS) generation and disrupts the formation of ERα/ERβ heterodimers [18][19][20]. Tributyltin (TBT), another well-known MDC, induces β-cell dysfunction and demise as well as ROS production by a mechanism involving peroxisome proliferator-activated receptor γ (PPARγ) [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Screening of metabolism-disrupting chemicals on pancreatic α-cells using in vitro methods

Santos

Babiloni-Chust

Marroquí

et al. 2022

Preprint

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Metabolism-disrupting chemicals (MDCs) are endocrine disruptors with obesogenic and/or diabetogenic action. There is mounting evidence linking exposure to MDCs to increased susceptibility to diabetes. Despite the important role of glucagon in glucose homeostasis, there is little information on the effects of MDCs on alpha-cells. Furthermore, there are no methods to identify and test MDCs with the potential to alter alpha-cell viability and function. Here we used the mouse alpha-cell line alphaTC1-9 to evaluate the effects of MDCs on cell viability and glucagon secretion. We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 microM): bisphenol-A (BPA), tributyltin (TBT), perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS), and dichlorodiphenyldichloroethylene (DDE). Using two different approaches, MTT assay and DNA-binding dyes, we observed that BPA and TBT decreased alpha-cell viability via a mechanism that depends on the activation of estrogen receptors and PPARgamma, respectively. These two chemicals induced ROS production, but barely altered the expression of endoplasmic reticulum (ER) stress markers. Although PFOA, TPP, TCS, and DDE did not alter cell viability nor induced ROS generation or ER stress, all four compounds negatively affected glucagon secretion. Our findings suggest that alphaTC1-9 cells seem an appropriate model to test chemicals with metabolism-disrupting activity and that the improvement of the test methods proposed herein could be incorporated into protocols for the screening of diabetogenic MDCs.

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Section: α-Cell Viability Testssupporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Screening of metabolism-disrupting chemicals on pancreatic α-cells using in vitro methods

Santos

Babiloni-Chust

Marroquí

et al. 2022

Preprint

Self Cite

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“…High levels of E2 (pregnancy period) showed improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in female New Zealand obese mice ( 114 ). E2 protects β cells against different apoptotic insults such as STZ and proinflammatory cytokines, and this effect is mediated in part through three estrogen receptors (ERα, ERβ and G protein-coupled estrogen receptor) ( 37 ). Considering the systemic nature of estrogenic effects and the multifaceted nature of intracellular hormonal signaling, long-term estrogen administration is undesirable in young newly diagnosed T1DM patients because of the adverse effects on the reproductive system that are associated with long-term estrogen administration.…”

Section: Effects Of Lipids On T1dmmentioning

confidence: 99%

Lipid metabolism in type 1 diabetes mellitus: Pathogenetic and therapeutic implications

Zhang

Xiao

et al. 2022

Front. Immunol.

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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with insulin deficiency due to pancreatic β cell destruction. Multiple independent cohort studies revealed specific lipid spectrum alterations prior to islet autoimmunity in T1DM. Except for serving as building blocks for membrane biogenesis, accumulative evidence suggests lipids and their derivatives can also modulate different biological processes in the progression of T1DM, such as inflammation responses, immune attacks, and β cell vulnerability. However, the types of lipids are huge and majority of them have been largely unexplored in T1DM. In this review, based on the lipid classification system, we summarize the clinical evidence on dyslipidemia related to T1DM and elucidate the potential mechanisms by which they participate in regulating inflammation responses, modulating lymphocyte function and influencing β cell susceptibility to apoptosis and dysfunction. This review systematically recapitulates the role and mechanisms of various lipids in T1DM, providing new therapeutic approaches for T1DM from a nutritional perspective.

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FTO-Nrf2 axis regulates bisphenol F-induced leydig cell toxicity in an m6A-YTHDF2-dependent manner

Zhou

Chen

et al. 2023

Environmental Pollution

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G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERα and ERβ in pancreatic beta cells

Cited by 24 publications

References 65 publications

Screening of metabolism-disrupting chemicals on pancreatic α-cells using in vitro methods

Screening of metabolism-disrupting chemicals on pancreatic α-cells using in vitro methods

Lipid metabolism in type 1 diabetes mellitus: Pathogenetic and therapeutic implications

FTO-Nrf2 axis regulates bisphenol F-induced leydig cell toxicity in an m6A-YTHDF2-dependent manner

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