Transcriptomic and Functional Analyses on the Effects of Dioxin on Insulin Secretion of Pancreatic Islets and β-Cells
| Autor: | Jing-Woei Li, Alice Hoi-Man Ng, Keng Po Lai, H. T. Wan, Ting-Fung Chan, Chris K C Wong |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Polychlorinated Dibenzodioxins Pyruvate dehydrogenase kinase medicine.medical_treatment Biology Dioxins Islets of Langerhans Mice 03 medical and health sciences Western blot Insulin-Secreting Cells Internal medicine medicine Animals Insulin Environmental Chemistry Secretion geography geography.geographical_feature_category medicine.diagnostic_test Pancreatic islets AMPK General Chemistry Islet Pyruvate dehydrogenase complex Glucose 030104 developmental biology Endocrinology medicine.anatomical_structure Environmental Pollutants |
| Zdroj: | Environmental Science & Technology. 51:11390-11400 |
| ISSN: | 1520-5851 0013-936X |
| DOI: | 10.1021/acs.est.7b02830 |
| Popis: | In this study, transcriptomic and Ingenuity Pathway Analysis (IPA) underlined that an ex-vivo TCDD treatment (0.1 nM) stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line (Min-6) validated the stimulatory effects of TCDD (0.1 and 1 nM) on basal-insulin secretion. At 0.1 nM TCDD treatment on Min-6, Western blot analysis showed activation of ERK1/2 and decreased expression of pyruvate dehydrogenase kinase (PDK). A reduction of PDK expression is associated with an increase of pyruvate dehydrogenase flux. This observation was supported by the detection of significantly higher cellular ATP levels, an increase of glucose-stimulated-insulin-secretion (GSIS), and an inhibition of the AMPK pathway. At 1 nM TCDD treatment on Min-6, significant inhibitions of the Akt-mTOR pathway, cellular ATP production, and GSIS were evident. The experimental studies in Min-6 supported the IPA of transcriptomic data in pancreatic islets. Collectively, TCDD treatment caused an elevated basal-insulin release in both islets and β-cell cultures. Moreover, our data revealed that the modulation of the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways might be an important component of the mechanism for the TCDD-perturbing effects on ATP production in β-cells in affecting insulin secretion. |
| Databáze: | OpenAIRE |
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