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Insulin Receptor Trafficking: Consequences for Insulin Sensitivity and Diabetes

School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia
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Int. J. Mol. Sci. 2019, 20(20), 5007; https://doi.org/10.3390/ijms20205007
Received: 28 August 2019 / Revised: 4 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Insulin Pathways for Therapeutic Intervention)
Insulin receptor (INSR) has been extensively studied in the area of cell proliferation and energy metabolism. Impaired INSR activities lead to insulin resistance, the key factor in the pathology of metabolic disorders including type 2 diabetes mellitus (T2DM). The mainstream opinion is that insulin resistance begins at a post-receptor level. The role of INSR activities and trafficking in insulin resistance pathogenesis has been largely ignored. Ligand-activated INSR is internalized and trafficked to early endosome (EE), where INSR is dephosphorylated and sorted. INSR can be subsequently conducted to lysosome for degradation or recycled back to the plasma membrane. The metabolic fate of INSR in cellular events implies the profound influence of INSR on insulin signaling pathways. Disruption of INSR-coupled activities has been identified in a wide range of insulin resistance-related diseases such as T2DM. Accumulating evidence suggests that alterations in INSR trafficking may lead to severe insulin resistance. However, there is very little understanding of how altered INSR activities undermine complex signaling pathways to the development of insulin resistance and T2DM. Here, we focus this review on summarizing previous findings on the molecular pathways of INSR trafficking in normal and diseased states. Through this review, we provide insights into the mechanistic role of INSR intracellular processes and activities in the development of insulin resistance and diabetes. View Full-Text
Keywords: insulin receptor; endocytosis; trafficking; recycling; insulin resistance insulin receptor; endocytosis; trafficking; recycling; insulin resistance
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Chen, Y.; Huang, L.; Qi, X.; Chen, C. Insulin Receptor Trafficking: Consequences for Insulin Sensitivity and Diabetes. Int. J. Mol. Sci. 2019, 20, 5007.

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