Figure 6.

Endothelial insulin signaling and the associated consequences in health (A) and diabetes (B). In non-diabetic/healthy individuals, insulin binds to its membrane receptor to preferentially activate, via the insulin receptor substrate (IRS), the phosphatidyl inositol 3-kinase (PI3-K) pathway leading to the induction of endothelial nitric oxide synthase (eNOS), increased production of nitric oxide (NO) and vascular smooth muscle (VSMC) dilation. In diabetes, insulin-induced activation of PI3-kinase and NO production is compromised whereas induction of MAP-kinase is maintained, leading to production of endothlin-1 (ET-1), VSMC constriction and decreased myofiber perfusion and hypertension. From Love et al., 2021 [54].