Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells
Abstract
:1. Introduction
2. Results
2.1. Hyperinsulinemia Impairs Endothelial Nitric Oxide Synthase in Microvascular Brain Endothelial Cells (MBECs) following Acute Insulin Stimulation
2.2. Insulin Receptor Internalization into MBECs Is Impaired with Hyperinsulinemia
2.3. Clathrin-Mediated Mechanisms Promote Insulin Receptor Internalization into MBECs and Become Impaired with Hyperinsulinemia
2.4. Hyperinsulinemia Reduces the Abundance of Downstream Trafficking Centers, Specifically after Insulin Stimulation
2.5. Stimulation of Hyperinsulinemic Cells with Insulin Disrupts the Phosphorylation Balance of Insulin Receptor Substrate 1 (IRS1) Residues Needed for Insulin Receptor Internalization
2.6. Hyperinsulinemia Reduces Src Homology Phosphatase 2 (SHP2) Activity and Disrupts the SHP2-IRS1 Binding Site
3. Discussion
4. Materials and Methods
4.1. Microvascular Endothelial Cell Culture
4.2. Flow Cytometry
4.3. Endocytosis Inhibitor Treatment
4.4. Western Immunoblotting
4.5. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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DiLucia, S.G.; Kendrick, B.J.; Sims-Robinson, C. Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells. Int. J. Mol. Sci. 2023, 24, 14670. https://doi.org/10.3390/ijms241914670
DiLucia SG, Kendrick BJ, Sims-Robinson C. Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells. International Journal of Molecular Sciences. 2023; 24(19):14670. https://doi.org/10.3390/ijms241914670
Chicago/Turabian StyleDiLucia, Stephanie G., B. Jacob Kendrick, and Catrina Sims-Robinson. 2023. "Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells" International Journal of Molecular Sciences 24, no. 19: 14670. https://doi.org/10.3390/ijms241914670