Exposure to Aroclor 1254 persistently suppresses the functions of pancreatic β-cells and deteriorates glucose homeostasis in male mice

Xi, Zhihui; Fang, Lü; Xu, Jing; Li, Bingshui; Zuo, Zhenghong; Lv, Liangju; Wang, Chonggang

doi:10.1016/j.envpol.2019.03.101

Cited by 18 publications

(20 citation statements)

References 74 publications

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“…A previous study indicated that the activation of peroxisome proliferator-activated receptor alpha (PPARα) via interacting with the aryl hydrocarbon receptor is a potential biological mechanism of the association between PCBs and diabetes [ 66 ]. Another research using animal subjects demonstrated that sub-chronic exposure to PCBs disrupted the glucose homeostasis, suppressed the functions of pancreatic β-cells and reduced the insulin levels in mice [ 54 ]. Although these mechanisms were not necessarily generalizable to GDM due to the significant physiological changes that occur during pregnancy, these results still provide relevant evidence to some extent.…”

Section: Discussionmentioning

confidence: 99%

Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

et al. 2022

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Objective To conduct a comprehensive systematic review and meta-analysis to estimate the relationship between endocrine-disrupting chemicals (EDCs), including polychlorinated biphenyls (PCBs), poly-brominated diphenyl ethers (PBDEs), phthalates (PAEs), and per- and polyfluoroalkyl substances (PFAS) exposure and risk of gestational diabetes mellitus (GDM). Methods Relevant studies from their inception to November 2021 were identified by searching EMBASE, PubMed, and Web of Science. The cohort and case–control studies that reported effect size with 95% confidence intervals (CIs) of EDC exposure and GDM were selected. The heterogeneity among the included studies was quantified by I2 statistic. Publication bias was evaluated through the Begg and Egger tests. Results Twenty-five articles with a total of 23,796 participants were found. Results indicated that exposure to PCBs has a significant influence on the incidence of GDM (OR = 1.14; 95% CI = 1.00-–1.31; n = 8). The risk of GDM was found to be associated with PBDE exposure (OR = 1.32; 95% CI = 1.15–1.53; n = 4). PAEs and PFASs exposure were also positively associated with the risk of GDM, with summary ORs of 1.10 (95% CI = 1.03–1.16; n = 7 for PAEs) and 1.09 (95% CI = 1.02–1.16; n = 11 for PFASs), respectively. When only cohort studies were considered, the summary OR between PCBs exposure and the risk of GDM was 0.99 (95% CI = 0.91–1.09; n = 5). Meanwhile, the summary ORs from cohort studies for PBDEs, PAEs, and PFASs exposure were 1.12 (95% CI = 1.00–1.26; n = 2), 1.08 (95% CI = 1.02–1.15; n = 5), and 1.06 (95% CI = 1.00–1.12; n = 8), respectively. The Beggs and Egger tests did not show publication bias, and the sensitivity analyses did not change the results in this meta-analysis. Conclusion These results support that exposure to certain EDCs, including PCBs, PBDEs, PAEs, and PFAS, increase the risk of GDM. Further large-sample epidemiologic researches and mechanistic studies are needed to verify the potential relationship and biological mechanisms. These results are of public health significance because the daily EDC exposure is expected to increase the risk of GDM development. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

et al. 2022

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“…In further support of this hypothesis, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress in islets of Langerhans, which is indicative of early β -cell failure [ 31 ]. PCBs exposure may directly result in failure of the β -cell mass to make sufficient levels of insulin [ 20 ]. PCBs also induce high levels of ROS and oxidative stress, suggesting that they may potentially induce damage in islet cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Culture and Cell Viability. Mouse islet β-TC-6 cells were seeded in 96-well culture plates and cultured with various concentrations of PCB118 (5,10,20,40,80,160, or 320 nmol/L), DMSO, and 15% fetal bovine serum for 48 hours or 72 hours. The Cell Counting Kit-8 (CCK8) was used to detect cell viability.…”

Section: Cellmentioning

confidence: 99%

“…Studies have shown that NLRP3 inflammasome activation plays an important role in the development of diabetes and diabetic complications [ 18 , 19 ]. Some studies have found that oral treatment with aroclor 1254, a PCB mixture, impairs glucose tolerance and results in the failure of β -cells to make sufficient levels of insulin in mice [ 20 ]. Exposure to PCB126 can result in deviant development of the pancreatic islet [ 21 ], and exposure to PCBs can induce high levels of ROS in islet cells [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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PCB118 Induces Inflammation of Islet Beta Cells via Activating ROS-NLRP3 Inflammasome Signaling

Jiang

Wang

Guo

et al. 2021

BioMed Research International

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Background. Diabetes mellitus is a clinical syndrome caused by genetic and environmental factors. Growing evidence suggests that exposure to environmental endocrine disruptors and activation of NLRP3 inflammasome signaling play a vital role in diabetes. However, it is unclear how PCB118, a common environmental endocrine disruptor, contributes to the incidence of diabetes, and its specific mechanism of action is unknown. In this study, we explored whether ROS-induced NLRP3 inflammasome priming and activation were related to PCB118 exposure in mouse islet β-TC-6 cells and the mechanisms of diabetes. Methods. Mouse islet β-TC-6 cells were cultured with PCB118 as a stimulating factor and ROS inhibitor N-acetyl cysteine (NAC) as an intervention. Cellular toxicity due to PCB118 was detected using the Cell Counting Kit-8; ROS was measured using DCFH-DA; the expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β protein were detected by western blot; and IL-6, IL-18, and C-C chemokine ligand 2 (CCL-2) were measured by ELISA. Results. PCB118 caused significant toxicity to the cells when the stimulation concentration was equal to or greater than 80 nmol/L at 72 hours ( p < 0.05 ) and increased the levels of ROS, NLRP3, caspase-1, IL-1β, IL-6, IL-18, and CCL-2 ( p < 0.05 ); the expressions of procaspase-1 and pro-IL-1β were downregulated in a dose-dependent manner after PCB118 exposure ( p < 0.05 ), which was prevented by pretreatment with NAC ( p < 0.05 ). Conclusions. PCB118 can activate NLRP3 inflammasome signaling in islet beta cells via the oxidative stress pathway and cause inflammation in islet beta cells. It suggests that environmental endocrine disruptors play an important role in the inflammation of islet beta cells and may contribute to the development of diabetes through NLRP3 inflammatory signaling.

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“…DOHaD clearly demonstrates the link between the adverse intrauterine environment and the risk for chronic metabolic consequences, including obesity, insulin resistance and cardiovascular disease, and such an effect may persist for generations through epigenetic mechanisms (7)(8)(9), including DNA methylation, histone modifications and non-coding RNAs (8). Epigenetic modifications are easily affected by environmental factors, such as tobacco smoking (10,11), environmental toxins (12,13), low-dose radiation (14), lack of physical activity (15)(16)(17), psychological stress (18), and circadian dysregulation (19,20).…”

Section: Introductionmentioning

confidence: 99%

The Effect and Potential Mechanism of Maternal Micronutrient Intake on Offspring Glucose Metabolism: An Emerging Field

Zhang

Xiao

2021

Front. Nutr.

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Diabetes has become the most common metabolic disease around the world. In addition to genetic and environmental factors in adulthood, the early life environment is critical to the progression of diabetes in adults, especially the environment during the fetal period; this concept is called “fetal programming.” Substantial evidence has illustrated the key role of early life macronutrient in programming metabolic diseases. Recently, the effect of maternal micronutrient intake on offspring glucose metabolism during later life has become an emerging field. This review focuses on updated human and animal evidence about the effect of maternal micronutrient status on offspring glucose metabolism and the underlying mechanism.

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Exposure to Aroclor 1254 persistently suppresses the functions of pancreatic β-cells and deteriorates glucose homeostasis in male mice

Cited by 18 publications

References 74 publications

Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

PCB118 Induces Inflammation of Islet Beta Cells via Activating ROS-NLRP3 Inflammasome Signaling

The Effect and Potential Mechanism of Maternal Micronutrient Intake on Offspring Glucose Metabolism: An Emerging Field

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