Insulin Actions on the Vascular Tissues: Physiological Effects and Pathophysiological Contributions to Vascular Complications of Diabetes.

Abstract 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 on 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 will 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, or of insulin structure or the various steps of its signaling pathways, since other articles in this issue will be discussing these areas in depth.