Upper panel: Summary of the pathway by which insulin binds to and activates its receptor, thereby enhancing signaling through the phosphatidylinositol-3
kinase (PI-3-K) Akt pathway to phosphorylate endothelial NOS (eNOS) and increase its enzymatic activity, augmenting the production
of NO. NO can readily diffuse to nearby smooth muscle cells (SMCs) and act both to increase the production of cyclic GMP and
to directly nitrosylate specific proteins to promote smooth muscle relaxation. Lower panel: Effect of this relaxation on resistance and terminal arterioles is illustrated. Relaxing the former can increase overall
blood flow, while relaxing the latter increases the number of capillaries perfused within the tissue (indicated by the increased
numbers of red capillaries in the right panel) at any one time. It should be noted that this is a dynamic process, and because of flowmotion, the particular capillaries
that are perfused at any time will vary over time scales from 2 to 40 s. IRS, insulin receptor substrate.