| 1. |
- Alonso-Magdalena, Paloma, et al.
(författare)
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Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2015-2025
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Tidskriftsartikel (refereegranskat)abstract
- The estrogen receptor beta (ER beta) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ER beta selective agonist WAY200070 as an insulinotropic molecule. We demonstrate that WAY200070 enhances glucose-stimulated insulin secretion both in mouse and human islets. In vivo experiments showed that a single administration of WAY200070 leads to an increase in plasma insulin levels with a concomitant improved response to a glucose load. Two-week treatment administration increased glucose-induced insulin release and pancreatic beta-cell mass and improved glucose and insulin sensitivity. In addition, streptozotocin-nicotinamide-induced diabetic mice treated with WAY200070 exhibited a significant improvement in plasma insulin levels and glucose tolerance as well as a regeneration of pancreatic beta-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic beta-cell mass. We conclude that ER beta agonists should be considered as new targets for the treatment of diabetes.
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| 2. |
- Legler, Juliette, et al.
(författare)
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The GOLIATH Project : Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:10
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.
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| 3. |
- Lind, Lars, et al.
(författare)
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Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:5, s. A81-A83
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Tidskriftsartikel (refereegranskat)abstract
- From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8–9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.
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| 4. |
- Muncke, Jane, et al.
(författare)
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A vision for safer food contact materials: Public health concerns as drivers for improved testing
- 2023
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Ingår i: ENVIRONMENT INTERNATIONAL. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. Toidentify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.
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| 5. |
- Muncke, Jane, et al.
(författare)
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Impacts of food contact chemicals on human health : a consensus statement
- 2020
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
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| 6. |
- Soriano, Sergi, et al.
(författare)
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Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor beta
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic beta-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ER beta(-/-) mice to study whether ER beta is involved in the rapid regulation of K-ATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in beta-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K-ATP channel activity, increased glucose-induced [Ca2+](i) signals and insulin release in beta-cells from WT mice but not in cells from ER beta(-/-) mice. The rapid reduction in the K-ATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ER beta and indicate that results obtained with BPA in mouse beta-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.
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| 7. |
- Zoeller, R. Thomas, 1952-, et al.
(författare)
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Update on Activities in Endocrine Disruptor Research and Policy
- 2019
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Ingår i: Endocrinology. - : Oxford University Press. - 0013-7227 .- 1945-7170. ; 160:7, s. 1681-1683
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Tidskriftsartikel (refereegranskat)abstract
- For nearly 15 years, the Endocrine Society has engaged in a coordinated effort to engage the issue of endocrine-disrupting chemicals (EDCs). This effort is based on an effective collaboration between scientists and physician members of the Endocrine Society and a competent and professional staff that supports membership efforts to study EDC actions and translate this knowledge to regulatory agencies. This is a brief history of these important efforts to inform the broad readership of Endocrinology.
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