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Cited by 6Mycotoxins in Agriculture and FoodNatural Antidiabetic Agents StudiesDiet, Metabolism, and Disease

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

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Pillay, Yashodani, Nagiah, Savania, Chuturgoon, Anil·2023·Toxins
DOI 10.3390/toxins15040244PMC PMC10145496
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Abstract

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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  • HepG2 cells are characterized by reduced sensitivity to insulin (insulin resistance) under TNFα, high glucose, or prolonged insulin stimulation, with reduced phosphorylation of IR, IRS-1, and Akt, leading to impaired insulin-stimulated glucose uptake and glycogen synthesis.

    “HepG2 cells are characterized by reduced sensitivity to insulin (insulin resistance), which has been demonstrated in numerous studies using models induced by tumor necrosis factor-α (TNFα), high glucose concentrations, or prolonged insulin stimulation [119,120,121].”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [121]

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Authors
Pillay, Y., Nagiah, S., & Chuturgoon, A.
Affiliations
University of KwaZulu-Natal (ZA)
Corresponding author
  • Pillay, Yashodani
  • Chuturgoon, Anil
ORCID
Venue
Toxins
Publisher
MDPI AG
Published
2023-03-27
Volume
15
Issue
4
Pages
244
ISSN
2072-6651 (ISSN-L)
DOI
10.3390/toxins15040244
PMC
PMC10145496
OpenAlex
W4361006814
Cited by
6
References
44
Citations by year
2026: 3 · 2025: 3
FWCI
0.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxins (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Nelson Mandela University Research Repository (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation (98323)
  • University of KwaZulu-Natal College of Health Science (98323)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycotoxins in Agriculture and Food
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
patulin, mycotoxins, insulin signaling, insulin resistance, pyruvate dehydrogenase complex, metabolic flexibility, hyperglycemia, type 2 diabetes, carbohydrate metabolism, HepG2 cells, HEK293 cells, non-communicable diseases, fruit contamination
MeSH terms
Animals, Diabetes Mellitus, Type 2, Humans, Insulin, Patulin, Signal Transduction, HEK293 Cells

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