Insulin's actions on vascular tissues: Physiological effects and pathophysiological contributions to vascular complications of diabetes

Background: Insulin has been demonstrated to exert direct and indirect effects on vascular tissues. Its actions in vascular cells are mediated by two major pathways: the insulin receptor substrate 1/2-phosphoinositide-3 kinase/Akt (IRS1/2/PI3K/Akt) pathway and the Src/mitogen-activated protein kinase (MAPK) pathway, both of which contribute to the expression and distribution of metabolites, hormones, and cytokines. Scope of review: In this review, we summarize the current understanding of insulin's physiological and pathophysiological actions and associated signaling pathways in vascular cells, mainly in endothelial cells (EC) and vascular smooth muscle cells (VSMC), and how these processes lead to selective insulin resistance. We also describe insulin's potential new signaling and biological effects derived from animal studies and cultured capillary and arterial EC, VSMC, and pericytes. We will not provide a detailed discussion of insulin's effects on the myocardium, insulin's structure, or its signaling pathways' various steps, since other articles in this issue discuss these areas in depth. Major conclusions: Insulin mediates many important functions on vascular cells via its receptors and signaling cascades. Its direct actions on EC and VSMC are important for transporting and communicating nutrients, cytokines, hormones, and other signaling molecules. These vascular actions are also important for regulating systemic fuel metabolism and energetics. Inhibiting or enhancing these pathways leads to selective insulin resistance, exacerbating the development of endothelial dysfunction, atherosclerosis, restenosis, poor wound healing, and even myocardial dysfunction. Targeted therapies to improve selective insulin resistance in EC and VSMC are thus needed to specifically mitigate these pathological processes. (C) 2021 The Authors. Published by Elsevier GmbH.

Automated summary

This review provides a comprehensive summary of insulin's physiological and pathophysiological actions, as well as the associated signaling pathways in vascular cells, particularly in endothelial cells and vascular smooth muscle cells. Insulin plays important roles in regulating nutrient transport and communication in vascular cells through its receptors and signaling cascades, affecting systemic fuel metabolism and energetics. Targeted therapies to improve selective insulin resistance in endothelial cells and vascular smooth muscle cells are necessary to mitigate pathological processes such as endothelial dysfunction, atherosclerosis, and myocardial dysfunction.