Version 1
: Received: 15 October 2024 / Approved: 15 October 2024 / Online: 15 October 2024 (09:07:08 CEST)
How to cite:
Im, S.; Kang, S.; Son, W. J.; Son, M.; Oh, S. J.; Yoon, H. J.; Pak, Y. K. Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes. Preprints2024, 2024101175. https://doi.org/10.20944/preprints202410.1175.v1
Im, S.; Kang, S.; Son, W. J.; Son, M.; Oh, S. J.; Yoon, H. J.; Pak, Y. K. Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes. Preprints 2024, 2024101175. https://doi.org/10.20944/preprints202410.1175.v1
Im, S.; Kang, S.; Son, W. J.; Son, M.; Oh, S. J.; Yoon, H. J.; Pak, Y. K. Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes. Preprints2024, 2024101175. https://doi.org/10.20944/preprints202410.1175.v1
APA Style
Im, S., Kang, S., Son, W. J., Son, M., Oh, S. J., Yoon, H. J., & Pak, Y. K. (2024). Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes. Preprints. https://doi.org/10.20944/preprints202410.1175.v1
Chicago/Turabian Style
Im, S., Hye Ji Yoon and Youngmi Kim Pak. 2024 "Dioxin-Induced PAI-1 Expression: A Novel Pathway to Pancreatic β-Cell Failure in Type 2 Diabetes" Preprints. https://doi.org/10.20944/preprints202410.1175.v1
Abstract
Exposure to environment polluting chemicals (EPCs), which are ligands of the aryl hydrocarbon receptor (AhR), is associated with the development of type 2 diabetes (T2D). This study explores the mechanisms by which AhR ligands contribute to β-cell failure in T2D. Incubation of rat RINm5F pancreatic β-cells with low-dose 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent AhR ligand, inhibited glucose-stimulated insulin secretion (GSIS). A single injection of TCDD in wild type mice reduced the size of Langerhans islets, but not in AhR liver knock-out mice (AhR-LKO). RNA-seq database analysis identified Serpine1, encoding for plasminogen activator inhibitor type-1 (PAI-1) as a TCDD-mediated secretory protein that are synthesized in an AhR-dependent manner in the liver. Elevated PAI-1 levels were shown to induce caspase 3/7-dependent apoptosis in RINm5F cells, suggesting a novel pathway through which EPCs exacerbate T2D. These findings support the hypothesis that chronic exposure to AhR ligands may directly inhibit GSIS in pan-creatic β-cells and indirectly induced β-cell apoptosis through increased PAI-1. This study provides new insights into the EPC-PAI-1 axis as a missing link between pancreatic β-cell failure and the progression of T2D and offers a potential target for therapeutic intervention.
Keywords
diabetes; AhR; TCDD; PAI-1; β-cell failure
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
