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Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells

Non-communicable diseases (NCDs) have risen rapidly worldwide, sparking interest in causative agents and pathways. Patulin (PAT), a xenobiotic found in fruit products contaminated by molds, is postulated to be diabetogenic in animals, but little is known about these effects in humans. This study exa...

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Autores principales: Pillay, Yashodani, Nagiah, Savania, Chuturgoon, Anil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145496/
https://www.ncbi.nlm.nih.gov/pubmed/37104182
http://dx.doi.org/10.3390/toxins15040244
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author Pillay, Yashodani
Nagiah, Savania
Chuturgoon, Anil
author_facet Pillay, Yashodani
Nagiah, Savania
Chuturgoon, Anil
author_sort Pillay, Yashodani
collection PubMed
description Non-communicable diseases (NCDs) have risen rapidly worldwide, sparking interest in causative agents and pathways. Patulin (PAT), a xenobiotic found in fruit products contaminated by molds, is postulated to be diabetogenic in animals, but little is known about these effects in humans. This study examined the effects of PAT on the insulin signaling pathway and the pyruvate dehydrogenase complex (PDH). HEK293 and HepG2 cells were exposed to normal (5 mM) or high (25 mM) glucose levels, insulin (1.7 nM) and PAT (0.2 μM; 2.0 μM) for 24 h. The qPCR determined gene expression of key enzymes involved in carbohydrate metabolism while Western blotting assessed the effects of PAT on the insulin signaling pathway and Pyruvate Dehydrogenase (PDH) axis. Under hyperglycemic conditions, PAT stimulated glucose production pathways, caused defects in the insulin signaling pathway and impaired PDH activity. These trends under hyperglycemic conditions remained consistent in the presence of insulin. These findings are of importance, given that PAT is ingested with fruit and fruit products. Results suggest PAT exposure may be an initiating event in insulin resistance, alluding to an etiological role in the pathogenesis of type 2 diabetes and disorders of metabolism. This highlights the importance of both diet and food quality in addressing the causes of NCDs.
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spelling pubmed-101454962023-04-29 Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells Pillay, Yashodani Nagiah, Savania Chuturgoon, Anil Toxins (Basel) Article Non-communicable diseases (NCDs) have risen rapidly worldwide, sparking interest in causative agents and pathways. Patulin (PAT), a xenobiotic found in fruit products contaminated by molds, is postulated to be diabetogenic in animals, but little is known about these effects in humans. This study examined the effects of PAT on the insulin signaling pathway and the pyruvate dehydrogenase complex (PDH). HEK293 and HepG2 cells were exposed to normal (5 mM) or high (25 mM) glucose levels, insulin (1.7 nM) and PAT (0.2 μM; 2.0 μM) for 24 h. The qPCR determined gene expression of key enzymes involved in carbohydrate metabolism while Western blotting assessed the effects of PAT on the insulin signaling pathway and Pyruvate Dehydrogenase (PDH) axis. Under hyperglycemic conditions, PAT stimulated glucose production pathways, caused defects in the insulin signaling pathway and impaired PDH activity. These trends under hyperglycemic conditions remained consistent in the presence of insulin. These findings are of importance, given that PAT is ingested with fruit and fruit products. Results suggest PAT exposure may be an initiating event in insulin resistance, alluding to an etiological role in the pathogenesis of type 2 diabetes and disorders of metabolism. This highlights the importance of both diet and food quality in addressing the causes of NCDs. MDPI 2023-03-27 /pmc/articles/PMC10145496/ /pubmed/37104182 http://dx.doi.org/10.3390/toxins15040244 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pillay, Yashodani
Nagiah, Savania
Chuturgoon, Anil
Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title_full Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title_fullStr Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title_full_unstemmed Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title_short Patulin Alters Insulin Signaling and Metabolic Flexibility in HepG2 and HEK293 Cells
title_sort patulin alters insulin signaling and metabolic flexibility in hepg2 and hek293 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145496/
https://www.ncbi.nlm.nih.gov/pubmed/37104182
http://dx.doi.org/10.3390/toxins15040244
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