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Article ; Online: The Commonly Overlooked Factor. Commentary on: "Environmental Obesogens and their Impact on Susceptibility to Obesity".

Alonso-Magdalena, Paloma / Nadal, Angel

2020 Volume 161, Issue 9

MeSH term(s)	Animals ; Dietary Supplements ; Kisspeptins ; Male ; Mice ; Mice, Knockout ; Obesity ; Spermatogenesis ; Spermatozoa ; Testosterone
Chemical Substances	Kiss1 protein, mouse ; Kisspeptins ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2020-10-11
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqaa123
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Article ; Online: Screening of Relevant Metabolism-Disrupting Chemicals on Pancreatic β-Cells: Evaluation of Murine and Human In Vitro Models.

Al-Abdulla, Ruba / Ferrero, Hilda / Soriano, Sergi / Boronat-Belda, Talía / Alonso-Magdalena, Paloma

International journal of molecular sciences

2022 Volume 23, Issue 8

Abstract: Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with the normal function of the endocrine system. EDCs are ubiquitous and can be found in a variety of consumer products such as food packaging materials, personal care and ... ...

Abstract	Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with the normal function of the endocrine system. EDCs are ubiquitous and can be found in a variety of consumer products such as food packaging materials, personal care and household products, plastic additives, and flame retardants. Over the last decade, the impact of EDCs on human health has been widely acknowledged as they have been associated with different endocrine diseases. Among them, a subset called metabolism-disrupting chemicals (MDCs) is able to promote metabolic changes that can lead to the development of metabolic disorders such as diabetes, obesity, hepatic steatosis, and metabolic syndrome, among others. Despite this, today, there are still no definitive and standardized in vitro tools to support the metabolic risk assessment of existing and emerging MDCs for regulatory purposes. Here, we evaluated the following two different pancreatic cell-based in vitro systems: the murine pancreatic β-cell line MIN6 as well as the human pancreatic β-cell line EndoC-βH1. Both were challenged with the following range of relevant concentrations of seven well-known EDCs: (bisphenol-A (BPA), bisphenol-S (BPS), bisphenol-F (BPF), perfluorooctanesulfonic acid (PFOS), di(2-ethylhexyl) phthalate (DEHP), cadmium chloride (CdCl
MeSH term(s)	Animals ; Benzhydryl Compounds ; Dichlorodiphenyl Dichloroethylene ; Endocrine Disruptors/toxicity ; Humans ; Insulin ; Mice ; Plastics
Chemical Substances	Benzhydryl Compounds ; Endocrine Disruptors ; Insulin ; Plastics ; Dichlorodiphenyl Dichloroethylene (4M7FS82U08)
Language	English
Publishing date	2022-04-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23084182
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Article ; Online: Exploring the Effects of Metabolism-Disrupting Chemicals on Pancreatic α-Cell Viability, Gene Expression and Function: A Screening Testing Approach.

Al-Abdulla, Ruba / Ferrero, Hilda / Boronat-Belda, Talía / Soriano, Sergi / Quesada, Iván / Alonso-Magdalena, Paloma

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Humans are constantly exposed to many environmental pollutants, some of which have been largely acknowledged as key factors in the development of metabolic disorders such as diabetes and obesity. These chemicals have been classified as endocrine- ... ...

Abstract	Humans are constantly exposed to many environmental pollutants, some of which have been largely acknowledged as key factors in the development of metabolic disorders such as diabetes and obesity. These chemicals have been classified as endocrine-disrupting chemicals (EDCs) and, more recently, since they can interfere with metabolic functions, they have been renamed as metabolism-disrupting chemicals (MDCs). MDCs are present in many consumer products, including food packaging, personal care products, plastic bottles and containers, and detergents. The scientific literature has ever-increasingly focused on insulin-releasing pancreatic β-cells as one of the main targets for MDCs. Evidence highlights that these substances may disrupt glucose homeostasis by altering pancreatic β-cell physiology. However, their potential impact on glucagon-secreting pancreatic α-cells remains poorly known despite the essential role that this cellular type plays in controlling glucose metabolism. In the present study, we have selected seven paradigmatic MDCs representing major toxic classes, including bisphenols, phthalates, perfluorinated compounds, metals, and pesticides. By using an in vitro cell-based model, the pancreatic α-cell line αTC1-9, we have explored the effects of these compounds on pancreatic α-cell viability, gene expression, and secretion. We found that cell viability was moderately affected after bisphenol-A (BPA), bisphenol-F (BPF), and perfluorooctanesulfonic acid (PFOS) exposure, although cytotoxicity was relatively low. In addition, all bisphenols, as well as di(2-ethylhexyl) phthalate (DEHP) and cadmium chloride (CdCl
MeSH term(s)	Humans ; Glucagon ; Cell Survival ; Environmental Pollutants/toxicity ; Insulin ; Benzhydryl Compounds/toxicity ; Endocrine Disruptors/toxicity ; Gene Expression
Chemical Substances	Glucagon (9007-92-5) ; Environmental Pollutants ; Insulin ; Benzhydryl Compounds ; bisphenol A (MLT3645I99) ; Endocrine Disruptors
Language	English
Publishing date	2023-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021044
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Article ; Online: The pancreatic β-cell in ageing: Implications in age-related diabetes.

Tudurí, Eva / Soriano, Sergi / Almagro, Lucía / Montanya, Eduard / Alonso-Magdalena, Paloma / Nadal, Ángel / Quesada, Ivan

Ageing research reviews

2022 Volume 80, Page(s) 101674

Abstract: The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt β-cell mass and function in the setting of insulin resistance and ... ...

Abstract	The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt β-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic β-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of β-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as β-cell proliferation, apoptosis and cell identity that can influence β-cell mass. Age-related changes also affect β-cell function at distinct steps including electrical activity, Ca
MeSH term(s)	Aging/metabolism ; Animals ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Insulin/metabolism ; Insulin Resistance ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Mice
Chemical Substances	Insulin
Language	English
Publishing date	2022-06-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2022.101674
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Article ; Online: ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors.

Crouzet, Thibault / Grignard, Elise / Brion, François / Blanc, Etienne B / Podechard, Normand / Langouet, Sophie / Alonso-Magdalena, Paloma / Hubert, Philippe / Kim, Min Ji / Audouze, Karine

Environment international

2023 Volume 174, Page(s) 107910

Abstract: Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs ... ...

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
MeSH term(s)	Animals ; Endocrine Disruptors/toxicity ; Endocrine Disruptors/metabolism ; In Vitro Techniques
Chemical Substances	Endocrine Disruptors
Language	English
Publishing date	2023-03-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107910
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Zs.A 3131: Show issues

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Article ; Online: ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors

Crouzet, Thibault / Grignard, Elise / Brion, François / Blanc, Etienne B. / Podechard, Normand / Langouet, Sophie / Alonso-Magdalena, Paloma / Hubert, Philippe / Kim, Min-ji / Audouze, Karine

Environment International. 2023 Apr., v. 174 p.107910-

2023

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
Keywords	environment ; fish ; questionnaires ; reproductive system ; Endocrine disrupting chemicals ; Zebrafish embryo ; OBERON ; Pepper ; Validation process ; IATA ; OECD
Language	English
Dates of publication	2023-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107910
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Effects of Aging on Male Mouse Pancreatic β-Cell Function Involve Multiple Events in the Regulation of Secretion: Influence of Insulin Sensitivity.

Tudurí, Eva / Soriano, Sergi / Almagro, Lucía / García-Heredia, Anabel / Rafacho, Alex / Alonso-Magdalena, Paloma / Nadal, Ángel / Quesada, Ivan

The journals of gerontology. Series A, Biological sciences and medical sciences

2021 Volume 77, Issue 3, Page(s) 405–415

Abstract: Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β cells undergo adaptive responses to increase ... ...

Abstract	Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of β-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on β-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized into 2 groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant, and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated β cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca2+ currents were higher in aged-LIS β cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented β-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural β-cell changes. Altogether, these findings indicate that aged mouse β cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on β cells.
MeSH term(s)	Aging ; Animals ; Calcium ; Diabetes Mellitus, Type 2 ; Glucose ; Insulin/pharmacology ; Insulin Resistance ; Insulin-Secreting Cells ; Islets of Langerhans/physiology ; Male ; Mice
Chemical Substances	Insulin ; Glucose (IY9XDZ35W2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glab276
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Article ; Online: ReadEDTest

Thibault Crouzet / Elise Grignard / François Brion / Etienne B. Blanc / Normand Podechard / Sophie Langouet / Paloma Alonso-Magdalena / Philippe Hubert / Min Ji Kim / Karine Audouze

Environment International, Vol 174, Iss , Pp 107910- (2023)

A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors

2023

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
Keywords	Endocrine disrupting chemicals ; Zebrafish embryo ; OBERON ; Pepper ; Validation process ; IATA ; Environmental sciences ; GE1-350
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse.

Quesada-Candela, Cristina / Tudurí, Eva / Marroquí, Laura / Alonso-Magdalena, Paloma / Quesada, Ivan / Nadal, Ángel

Metabolism: clinical and experimental

2019 Volume 102, Page(s) 153963

Abstract: Background: Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and ... ...

Abstract	Background: Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and seem to be involved in gestational diabetes, there is no information about their potential adaptations or changes during pregnancy. Material and methods: Non-pregnant (controls) and pregnant C57BL/6 mice at gestational day 18.5 (G18.5) and their isolated pancreatic islets were used for in vivo and ex vivo studies, respectively. The effect of pregnancy hormones was tested in glucagon-secreting α-TC1.9 cells. Immunohistochemical analysis was performed in pancreatic slices. Glucagon gene expression was monitored by RT-qPCR. Glucagon secretion and plasma hormones were measured by ELISA. Results: Pregnant mice on G18.5 exhibited alpha-cell hypertrophy as well as augmented alpha-cell area and mass. This alpha-cell mass expansion was mainly due to increased proliferation. No changes in alpha-cell apoptosis, ductal neogenesis, or alpha-to-beta transdifferentiation were found compared with controls. Pregnant mice on G18.5 exhibited hypoglucagonemia. Additionally, in vitro glucagon secretion at low glucose levels was decreased in isolated islets from pregnant animals. Glucagon content was also reduced. Experiments in α-TC1.9 cells indicated that, unlike estradiol and progesterone, placental lactogens and prolactin stimulated alpha-cell proliferation. Placental lactogens, prolactin and estradiol also inhibited glucagon release from α-TC1.9 cells at low glucose levels. Conclusions: The pancreatic alpha-cell in mice undergoes several morphofunctional changes during late pregnancy, which may contribute to proper glucose homeostasis. Gestational hormones are likely involved in these processes.
MeSH term(s)	Adaptation, Physiological/physiology ; Animals ; Cell Count ; Cell Size ; Cells, Cultured ; Female ; Gestational Age ; Glucagon/metabolism ; Glucagon-Secreting Cells/cytology ; Glucagon-Secreting Cells/physiology ; Islets of Langerhans/cytology ; Islets of Langerhans/physiology ; Mice ; Mice, Inbred C57BL ; Placental Hormones/physiology ; Pregnancy
Chemical Substances	Placental Hormones ; Glucagon (9007-92-5)
Language	English
Publishing date	2019-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80230-x
ISSN	1532-8600 ; 0026-0495
ISSN (online)	1532-8600
ISSN	0026-0495
DOI	10.1016/j.metabol.2019.153963
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Article ; Online: Corrigendum to "In utero exposure to bisphenol-A disrupts key elements of retinoid system in male mice offspring".

Esteban, Javier / Serrano-Maciá, Marina / Sánchez-Perez, Ismael / Alonso-Magdalena, Paloma / Pellín, María de la Cruz / García-Arévalo, Marta / Nadal, Ángel / Barril, Jose

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2021 Volume 158, Page(s) 112556

Language	English
Publishing date	2021-09-20
Publishing country	England
Document type	Published Erratum
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2021.112556
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