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Original Article
- Endocrine Research
- Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells
- Seok-Woo Hong, Jinmi Lee, Min Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
- Endocrinol Metab. 2020;35(4):943-953. Published online December 2, 2020
- DOI: https://doi.org/10.3803/EnM.2020.768
- 5,664 View
- 135 Download
- 4 Web of Science
- 6 Crossref
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Abstract
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Supplementary Material
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ePub - Background
There is a great need to discover factors that could protect pancreatic β-cells from apoptosis and thus prevent diabetes mellitus. Clusterin (CLU), a chaperone protein, plays an important role in cell protection in numerous cells and is involved in various cellular mechanisms, including autophagy. In the present study, we investigated the protective role of CLU through autophagy regulation in pancreatic β-cells.
Methods
To identify the protective role of CLU, mouse insulinoma 6 (MIN6) cells were incubated with CLU and/or free fatty acid (FFA) palmitate, and cellular apoptosis and autophagy were examined.
Results
Treatment with CLU remarkably upregulated microtubule-associated protein 1-light chain 3 (LC3)-II conversion in a doseand time-dependent manner with a significant increase in the autophagy-related 3 (Atg3) gene expression level, which is a mediator of LC3-II conversion. Moreover, co-immunoprecipitation and fluorescence microscopy experiments showed that the molecular interaction of LC3 with Atg3 and p62 was markedly increased by CLU. Stimulation of LC3-II conversion by CLU persisted in lipotoxic conditions, and FFA-induced apoptosis and dysfunction were simultaneously improved by CLU treatment. Finally, inhibition of LC3-II conversion by Atg3 gene knockdown markedly attenuated the cytoprotective effect of CLU.
Conclusion
Taken together, these findings suggest that CLU protects pancreatic β-cells against lipotoxicity-induced apoptosis via autophagy stimulation mediated by facilitating LC3-II conversion. Thus, CLU has therapeutic effects on FFA-induced pancreatic β-cell dysfunction. -
Citations
Citations to this article as recorded by
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Alexandra Coomans de Brachène, Corentin Scoubeau, Anyïshai E. Musuaya, Jose Maria Costa-Junior, Angela Castela, Julie Carpentier, Vitalie Faoro, Malgorzata Klass, Miriam Cnop, Decio L. Eizirik
Diabetologia.2023; 66(3): 450. CrossRef - Apolipoprotein J Attenuates Vascular Restenosis by Promoting Autophagy and Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells
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Journal of Cardiovascular Translational Research.2022; 15(5): 1086. CrossRef - Targets for rescue from fatty acid-induced lipotoxicity in pancreatic beta cells
Seok-Woo Hong, Won-Young Lee
Cardiovascular Prevention and Pharmacotherapy.2022; 4(2): 57. CrossRef - Co-regulators of autophagy and the cell cycle in HFD − As treated mice
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Journal of Trace Elements and Minerals.2022; 2: 100018. CrossRef - Targeting pancreatic β cells for diabetes treatment
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Nature Metabolism.2022; 4(9): 1097. CrossRef - Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies
Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
International Journal of Molecular Sciences.2021; 22(10): 5303. CrossRef
- Exercise as a non-pharmacological intervention to protect pancreatic beta cells in individuals with type 1 and type 2 diabetes
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