scholarly journals Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 525 ◽  
Author(s):  
Tiziana Filardi ◽  
Francesca Panimolle ◽  
Andrea Lenzi ◽  
Susanna Morano
Keyword(s):  
Bisphenol A ◽  
Pregnancy Complications ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Preventive Measure ◽  
Adverse Outcomes ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction

Endocrine-disrupting chemicals (EDCs) are exogenous substances that are able to interfere with hormone action, likely contributing to the development of several endocrine and metabolic diseases. Among them, Bisphenol A (BPA) and phthalates contaminate food and water and have been largely studied as obesogenic agents. They might contribute to weight gain, insulin resistance and pancreatic β-cell dysfunction in pregnancy, potentially playing a role in the development of pregnancy complications, such as gestational diabetes mellitus (GDM), and adverse outcomes. Pregnancy and childhood are sensitive windows of susceptibility, and, although with not univocal results, preclinical and clinical studies have suggested that exposure to BPA and phthalates at these stages of life might have an impact on the development of metabolic diseases even many years later. The molecular mechanisms underlying this association are largely unknown, but adipocyte and pancreatic β-cell dysfunction are suspected to be involved. Remarkably, transgenerational damage has been observed, which might be explained by epigenetic changes. Further research is needed to address knowledge gaps and to provide preventive measure to limit health risks connected with exposure to EDCs.

Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes

2008 ◽  
Vol 36 (3) ◽  
pp. 348-352 ◽  
Author(s):  
Miriam Cnop
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Cell Loss ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction

The prevalence of Type 2 diabetes is increasing dramatically as a result of the obesity epidemic, and poses a major health and socio-economic burden. Type 2 diabetes develops in individuals who fail to compensate for insulin resistance by increasing pancreatic insulin secretion. This insulin deficiency results from pancreatic β-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified (‘free’) fatty acids]. In addition, they contribute to β-cell failure in genetically predisposed individuals. NEFAs cause β-cell apoptosis and may thus contribute to progressive β-cell loss in Type 2 diabetes. The molecular pathways and regulators involved in NEFA-mediated β-cell dysfunction and apoptosis are beginning to be understood. We have identified ER (endoplasmic reticulum) stress as one of the molecular mechanisms implicated in NEFA-induced β-cell apoptosis. ER stress was also proposed as a mechanism linking high-fat-diet-induced obesity with insulin resistance. This cellular stress response may thus be a common molecular pathway for the two main causes of Type 2 diabetes, namely insulin resistance and β-cell loss. A better understanding of the molecular mechanisms contributing to pancreatic β-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes.

Molecular mechanisms of lipotoxicity-induced pancreatic β-cell dysfunction

2021 ◽  
Author(s):  
Asier Benito-Vicente ◽  
Shifa Jebari-Benslaiman ◽  
Unai Galicia-Garcia ◽  
Asier Larrea-Sebal ◽  
Kepa B. Uribe ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

Piperine protects against pancreatic β-cell dysfunction by alleviating macrophage inflammation in obese mice

Life Sciences ◽  
2021 ◽  
pp. 119312
Author(s):  
Yanting Yuan ◽  
Ji Zhou ◽  
Ruixin Hu ◽  
Linhai Zou ◽  
Lixia Ji ◽  
...  
Keyword(s):  
Pancreatic Β Cell ◽  
Obese Mice ◽  
Β Cell ◽  
Cell Dysfunction

Molecular aspects of pancreatic β‐cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA

2018 ◽  
Vol 234 (6) ◽  
pp. 8411-8425 ◽  
Author(s):  
Mohammad Javad Saeedi Borujeni ◽  
Ebrahim Esfandiary ◽  
Azar Baradaran ◽  
Ali Valiani ◽  
Mustafa Ghanadian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Molecular Aspects

Dexamethasone induces pancreatic β-cell apoptosis through upregulation of TRAIL death receptor

2021 ◽  
Author(s):  
Kanchana Suksri ◽  
Namoiy Semprasert ◽  
Mutita Junking ◽  
Suchanoot Kutpruek ◽  
Thawornchai Limjindaporn ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Death Receptor ◽  
Caspase 8 ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Apoptotic Protein ◽  
Induced Apoptosis ◽  
Trail Death Receptor

Long-term medication with dexamethasone (a synthetic glucocorticoid (GC) drug) results in hyperglycemia, or steroid-induced diabetes. Although recent studies revealed dexamethasone directly induces pancreatic β-cell apoptosis, its molecular mechanisms remain unclear. In our initial analysis of mRNA transcripts, we discovered the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway may be involved in dexamethasone-induced pancreatic β-cell apoptosis. In the present study, a mechanism of dexamethasone-induced pancreatic β-cell apoptosis through the TRAIL pathway was investigated in cultured cells and isolated mouse islets. INS-1 cells were cultured with and without dexamethasone in the presence or absence of a glucocorticoid receptor (GR) inhibitor, RU486. We found that dexamethasone induced pancreatic β-cell apoptosis in association with the upregulation of TRAIL mRNA and protein expression. Moreover, dexamethasone upregulated the TRAIL death receptor (DR5) protein but suppressed the decoy receptor (DcR1) protein. Similar findings were observed in mouse isolated islets: dexamethasone increased TRAIL and DR5 compared to that of control mice. Furthermore, dexamethasone stimulated pro-apoptotic signaling including superoxide production, caspase-8, -9, and -3 activities, NF-B, and Bax, but repressed the anti-apoptotic protein, Bcl-2. All these effects were inhibited by the GR-inhibitor, RU486. Furthermore, knock down DR5 decreased dexamethasone-induced caspase 3 activity. Caspase-8 and caspase-9 inhibitors protected pancreatic β-cells from dexamethasone-induced apoptosis. Taken together, dexamethasone induced pancreatic β-cell apoptosis by binding to the GR and inducing DR5 and TRAIL pathway.

Effects of pharmacological inhibition of NADPH oxidase or iNOS on pro-inflammatory cytokine, palmitic acid or H2O2-induced mouse islet or clonal pancreatic β-cell dysfunction

2010 ◽  
Vol 30 (6) ◽  
pp. 445-453 ◽  
Author(s):  
Marta Michalska ◽  
Gabriele Wolf ◽  
Reinhard Walther ◽  
Philip Newsholme
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Nadph Oxidase ◽  
Inflammatory Cytokine ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Mouse Islets ◽  
Pro Inflammatory Cytokines

Various pancreatic β-cell stressors including cytokines and saturated fatty acids are known to induce oxidative stress, which results in metabolic disturbances and a reduction in insulin secretion. However, the key mechanisms underlying dysfunction are unknown. We investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines, H2O2 or PA (palmitic acid) on β-cell insulin secretion, ATP, the NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) component p47phox and iNOS (inducible nitric oxide synthase) levels using primary mouse islets or clonal rat BRIN-BD11 β-cells. Addition of a pro-inflammatory cytokine mixture [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] or H2O2 (at sub-lethal concentrations) inhibited chronic (24 h) levels of insulin release by at least 50% (from islets and BRIN-BD11 cells), while addition of the saturated fatty acid palmitate inhibited acute (20 min) stimulated levels of insulin release from mouse islets. H2O2 decreased ATP levels in the cell line, but elevated p47phox and iNOS levels as did cytokine addition. Similar effects were observed in mouse islets with respect to elevation of p47phox and iNOS levels. Addition of antioxidants SOD (superoxide dismutase), Cat (catalase) and NAC (N-acetylcysteine) attenuated H2O2 or the saturated fatty acid palmitate-dependent effects, but not cytokine-induced dysfunction. However, specific chemical inhibitors of NADPH oxidase and/or iNOS appear to significantly attenuate the effects of cytokines, H2O2 or fatty acids in islets. While pro-inflammatory cytokines are known to increase p47phox and iNOS levels in β-cells, we now report that H2O2 can increase levels of the latter two proteins, suggesting a key role for positive-feedback redox sensitive regulation of β-cell dysfunction.

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