Exposure of perfluorononanoic acid suppresses the hepatic insulin signal pathway and increases serum glucose in rats
Abstract
Exposure to perfluorononanoic acid (PFNA), an increasingly persistent organic pollutant that has been detected in abiotic and biotic matrices, has been demonstrated to cause hepatotoxicity in animals. However, the effects of PFNA on hepatic glucose metabolism have not been fully characterized. In this study, male rats were exposed to 0, 0.2, 1 or 5mg/kg/d PFNA for 14 days to explore the specific effect of PFNA on hepatic glycometabolism and its underlying mechanisms. The results showed that administration of 5mg/kg/d PFNA significantly increased serum glucose and hepatic glycogen in rats. Quantitative real-time PCR analysis showed that PFNA exposure changed the expression levels of several genes related to hepatic glucose metabolism, such as the glucose-6-phosphatase (G6PC) gene and the glucose transporter 2 (GLUT2) gene, which were upregulated, and the glucokinase (GCK) gene and the phosphoinositide-3-kinase, catalytic, alpha polypeptide (PI3Kca) gene, which were decreased. The protein expression levels of phospho-insulin receptor 1(IRS1), phospho-PI3K, phospho-AKT and phospho-phosphoinositide-dependent kinase 1 (PDK1) were decreased in the livers of rats that received 5mg/kg/d PFNA. The expression of phospho-glycogen synthase kinase-3 beta (GSK3β, Ser 9) was increased, which explains the augment of hepatic glycogen. Significant increases in hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA) were found in the livers of 5mg/kg/d PFNA-treated rats. Thus, exposure to PFNA d…
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Animal experiments have demonstrated that exposure to PFASs can induce metabolic disturbance and IR through inflammatory response and endocrine disruption, resulting in an increased incidence of T2D.
“Animal experiments have also demonstrated that exposure to PFASs can induce metabolic disturbance and IR through inflammatory response and endocrine disruption, resulting in an increased incidence of T2D (Dong et al., 2022; Fang et al., 2012; Yan et al., 2015).”
From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Fang et al., 2012
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- Authors
- Fang, X., Gao, G., Xue, H., Zhang, X., & Wang, H.
- Affiliations
- Dalian University of Technology (CN)
- Suzhou University (CN)
- Corresponding author
- Fang, Xuemei
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 294
- Issue
- 2-3
- Pages
- 109-115
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W1965560164
- Cited by
- 43
- References
- 2
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (11040606M44, 10040606Q65)
- Scientific Research Foundation of Suzhou University for Doctor (2011jb04)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- perfluorononanoic acid, PFNA, hepatic insulin signaling, hepatic glucose metabolism, serum glucose, liver glycogen, glucose-6-phosphatase, GLUT2, glucokinase, PI3K/Akt signaling, glycogen synthase kinase-3β, oxidative stress, hepatotoxicity, persistent organic pollutants
- MeSH terms
- Animals, Blood Glucose, Dose-Response Relationship, Drug, Fatty Acids, Fluorocarbons, Gene Expression Regulation, Glycogen, Hydrogen Peroxide, Insulin, Liver, Male, Malondialdehyde, Signal Transduction, Polymerase Chain Reaction, Rats, Sprague-Dawley, Oxidative Stress, Rats
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