The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance
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s41467-022-35176-7.pdf
Description
Published version
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5.26 MB
Format
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Checksum (MD5)
1741a4f17275aed5bb2c23637d99233b
Author(s)
Dall’Agnese, Alessandra
Platt, Jesse M
Zheng, Ming M
Friesen, Max
Dall’Agnese, Giuseppe
Blaise, Alyssa M
Spinelli, Jessica B
Henninger, Jonathan E
Tevonian, Erin N
Hannett, Nancy M
Date Issued
December 6, 2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Dall’Agnese, Alessandra, Platt, Jesse M, Zheng, Ming M, Friesen, Max, Dall’Agnese, Giuseppe et al. 2022. "The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance." Nature Communications, 13 (1).
Version
Final published version
Abstract
AbstractInsulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-022-35176-7
