| Autor: |
Myriam P. Hoyeck, Ma. Enrica Angela Ching, Lahari Basu, Kyle van Allen, Jana Palaniyandi, Ineli Perera, Emilia Poleo-Giordani, Antonio A. Hanson, Peyman Ghorbani, Morgan D. Fullerton, Jennifer E. Bruin |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 81, Iss , Pp 101893- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2024.101893 |
| Popis: |
Objective: Chronic exposure to persistent organic pollutants (POPs) is associated with increased incidence of type 2 diabetes, hyperglycemia, and poor insulin secretion in humans. Dioxins and dioxin-like compounds are a broad class of POPs that exert cellular toxicity through activation of the aryl hydrocarbon receptor (AhR). We previously showed that a single high-dose injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, aka dioxin; 20 μg/kg) in vivo reduced fasted and glucose-stimulated plasma insulin levels for up to 6 weeks in male and female mice. TCDD-exposed male mice were also modestly hypoglycemic and had increased insulin sensitivity, whereas TCDD-exposed females were transiently glucose intolerant. Whether these effects are driven by AhR activation in β-cells requires investigation. Methods: We exposed female and male β-cell specific Ahr knockout (βAhrKO) mice and littermate Ins1-Cre genotype controls (βAhrWT) to a single high dose of 20 μg/kg TCDD and tracked the mice for 6 weeks. Results: Under baseline conditions, deleting AhR from β-cells caused hypoglycemia in female mice, increased insulin secretion ex vivo in female mouse islets, and promoted modest weight gain in male mice. Importantly, high-dose TCDD exposure impaired glucose homeostasis and β-cell function in βAhrWT mice, but these phenotypes were largely abolished in TCDD-exposed βAhrKO mice. Conclusion: Our study demonstrates that AhR signaling in β-cells is important for regulating baseline β-cell function in female mice and energy homeostasis in male mice. We also show that β-cell AhR signaling largely mediates the effects of TCDD on glucose homeostasis in both sexes, suggesting that the effects of TCDD on β-cell function and health are driving metabolic phenotypes in peripheral tissues. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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