Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet β Cells via G Protein-Coupled Receptor 40
Open accessAbstract
The potential causal relationship between exposure to environmental contaminants and diabetes is troubling. Exposure of perfluoroalkyl substances (PFASs) is found to be associated with hyperinsulinemia and the enhancement of insulin secretion by islet β cells in humans, but the underlying mechanism is still unclear. Here, by combining in vivo studies with both wild type and gene knockout mice and in vitro studies with mouse islet β cells (β-TC-6), we demonstrated clearly that 1 h exposure of perfluorooctanesulfonate (PFOS) stimulated insulin secretion and intracellular calcium level by activating G protein-coupled receptor 40 (GPR40), a vital free fatty acid regulated membrane receptor on islet β cells. We further showed that the observed effects of PFASs on the mouse model may also exist in humans by investigating the molecular binding interaction of PFASs with human GPR40. We thus provided evidence for a novel mechanism for how insulin-secretion is disrupted by PFASs in humans.
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PFOS can stimulate insulin secretion and intracellular calcium level by activating G protein-coupled receptor 40 (GPR40).
“A recent study showed that PFOS can stimulate insulin”
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 Qin et al., 2020
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Self-citationStimulus-secretion coupling in pancreatic β cells
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- Authors
- Qin, W.-P., Cao, L.-Y., Li, C.-H., Guo, L.-H., Colbourne, J., & Ren, X.-M.
- Affiliations
- State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085, China
- Chinese Academy of Sciences (CN)
- China Jiliang University (CN)
- University of Birmingham (GB)
- Corresponding author
- Guo, Liang-Hong
- Venue
- Environmental Science & Technology
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-02-24
- Volume
- 54
- Issue
- 6
- Pages
- 3428-3436
- ISSN
- 0013-936X (ISSN-L)
- 1520-5851
- OpenAlex
- W3008632684
- Cited by
- 71
- References
- 4
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 14 · 2023: 8 · 2022: 13 · 2021: 8 · 2020: 1
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Environmental Science & Technology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion, other-oa)
- Funders
- Royal Society (IC160121)
- National Natural Science Foundation of China (21777187, 91543203)
- Chinese Academy of Sciences (QYZDJ-SSW-DQC020)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- perfluorinated compounds, PFOS, insulin secretion, pancreatic beta cells, intracellular calcium, hyperinsulinemia, diabetes mellitus, environmental pollutants, free fatty acid receptors, molecular binding
- MeSH terms
- Insulin Secretion, Animals, Fluorocarbons, Humans, Insulin, Islets of Langerhans, Receptors, G-Protein-Coupled, Insulin-Secreting Cells, Mice
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