Chapter 3 - Nonclassic effects of insulin: physiological actions on the vascular tissues and pathophysiological contributions to atherogenesis, mitogenesis, and restenosis

Abstract

Aside from its classic metabolic actions, insulin has been reported to exert cellular effects on many tissues. In this review, we will focus on insulin’s physiological and pathophysiological actions on vascular cells, mainly in endothelial cells and vascular smooth muscle cells (VSMC), as well as their effects on atherogenesis, mitogenesis, restenosis, and blood flow. In vascular cells, insulin’s actions are mediated chiefly by two pathways: The insulin receptor substrate1/2 and phosphoinositide-3 kinase/Akt pathway and the Src/mitogen-activated protein kinase pathway. Insulin also exerts direct actions on the vessel wall, endothelial cells, VSMC, and the basement membrane, which are critical for the transporting of nutrients, cytokines, hormones, and other signaling molecules. Chronic upregulation or downregulation of these pathways can trigger a cascade of downstream cellular signals and ultimately contribute to the development of vascular complications in diabetes, making these pathways potential targets for future therapies.