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The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance

Authors :
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
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
Lazaris, Charalampos
Drescher, Hannah K
Bartsch, Lea M
Kilgore, Henry R
Jaenisch, Rudolf
Griffith, Linda G
Cisse, Ibrahim I
Jeppesen, Jacob F
Lee, Tong I
Young, Richard A
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
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
Lazaris, Charalampos
Drescher, Hannah K
Bartsch, Lea M
Kilgore, Henry R
Jaenisch, Rudolf
Griffith, Linda G
Cisse, Ibrahim I
Jeppesen, Jacob F
Lee, Tong I
Young, Richard A
Source :
Nature
Publication Year :
2022

Abstract

<jats:title>Abstract</jats:title><jats:p>Insulin 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.</jats:p>

Details

Database :
OAIster
Journal :
Nature
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1370255881
Document Type :
Electronic Resource