Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species

Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancrea...

Full description

Saved in:

Bibliographic Details
Published in:	Islets Vol. 16; no. 1; p. 2361996
Main Authors:	van Allen, Kyle A, Gang, Noa, Hoyeck, Myriam P, Perera, Ineli, Zhang, Dahai, Atlas, Ella, Lynn, Francis C, Bruin, Jennifer E
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 31-12-2024
Subjects:	Animals Cells, Cultured Flame Retardants - toxicity Humans Hydrocarbons, Chlorinated - toxicity Insulin - metabolism Insulin Secretion - drug effects Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Male Mice Mice, Inbred C57BL Polycyclic Compounds - pharmacology Rats stem cells persistent organic pollutants Dechlorane Plus β-cells diabetes islets
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 μg/kg per day) and fed chow or high fat diet for 28-days . DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) using immortalized rat β-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of compared to GLT alone. Our study highlights the importance and challenges of using different models for studying chemical toxicity.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1938-2014 1938-2022
DOI:	10.1080/19382014.2024.2361996