Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.

Adequate perfusion of cerebral tissues, which is necessary for the preservation of optimal brain health, depends on insulin signaling within brain endothelial cells. Proper insulin signaling relies on the regulated internalization of insulin bound to the insulin receptor, a process which is disrupted by hyperinsulinemia via an unknown mechanism. Thus, the goal of this study was to characterize the impact of hyperinsulinemia on the regulation of molecular targets involved in cerebral blood flow and insulin receptor internalization into brain endothelial cells.