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Developmental exposure to a very low dose of bisphenol A induces persistent islet insulin hypersecretion in Fischer 344 rat offspring
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.ORCID iD: 0000-0002-8949-3555
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
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2019 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 172, p. 127-136Article in journal (Refereed) Published
Abstract [en]

Background: In children with obesity, accentuated insulin secretion has been coupled with development of type 2 diabetes mellitus (T2DM). Bisphenol A (BPA) is a chemical with endocrine- and metabolism-disrupting properties which can be measured in a majority of the population. Exposure to BPA has been associated with the development of metabolic diseases including T2DM.

Objective: The aim of this study was to investigate if exposure early in life to an environmentally relevant low dose of BPA causes insulin hypersecretion in rat offspring.

Methods: Pregnant Fischer 344 rats were exposed to 0.5 (BPA0.5) or 50 (BPA50) jig BPA/kg BW/day via drinking water from gestational day 3.5 until postnatal day 22. Pancreata from dams and 5- and 52-week-old offspring were procured and islets were isolated by collagenase digestion. Glucose-stimulated insulin secretion and insulin content in the islets were determined by ELISA.

Results: Basal (5.5 mM glucose) islet insulin secretion was not affected by BPA exposure. However, stimulated (11 mM glucose) insulin secretion was enhanced by about 50% in islets isolated from BPA0.5-exposed 5- and 52 week-old female and male offspring and by 80% in islets from dams, compared with control. In contrast, the higher dose, BPA50, reduced stimulated insulin secretion by 40% in both 5- and 52-week-old female and male offspring and dams, compared with control.

Conclusion: A BPA intake 8 times lower than the European Food Safety Authority's (EFSA's) current tolerable daily intake (TDI) of 4 mu g/kg BW/day of BPA delivered via drinking water during gestation and early development causes islet insulin hypersecretion in rat offspring up to one year after exposure. The effects of BPA exposure on the endocrine pancreas may promote the development of metabolic disease including T2DM.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2019. Vol. 172, p. 127-136
Keywords [en]
Bisphenol A, Endocrine disruptor, Fischer 344 rats, Insulin hypersecretion, Islets of Langerhans
National Category
Occupational Health and Environmental Health
Identifiers
URN: urn:nbn:se:uu:diva-387967DOI: 10.1016/j.envres.2019.02.009ISI: 000468377500014PubMedID: 30782532OAI: oai:DiVA.org:uu-387967DiVA, id: diva2:1331837
Funder
Swedish Research Council Formas, 216-2012-475Swedish Diabetes Association, DIA 2016-146Ernfors Foundation, 170504Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved

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