The renin-angiotensin system and diabetes: an update

Abstract

In the past few years the classical concept of the renin-angiotensin system (RAS) has experienced substantial conceptual changes. The identification of the renin/prorenin receptor, the angiotensin-converting enzyme homologue ACE2 as an angiotensin peptide processing enzyme, Mas as a receptor for Ang-(1-7) and the possibility of signaling through ACE, have contributed to switch our understanding of the RAS from the classical limited-proteolysis linear cascade to a cascade with multiple mediators, multiple receptors, and multi-functional enzymes. In this review we will focus on the recent findings related to RAS and, in particular, on its role in diabetes by discussing possible interactions between RAS mediators, endothelium function, and insulin signaling transduction pathways as well as the putative role of ACE2-Ang-(1-7)-Mas axis in disease pathogenesis.

Figure 1

Novel components of the renin–angiotensin system and its interactions. Abbreviations: Ang, angiotensin, AT₁, AT₂, angiotensinergic receptors types 1 and 2; NO, nitric oxide; ACE, angiotensin converting enzyme; ACE2, angiotensin-converting enzyme 2.

Figure 2

Interactions between angiotensin II and insulin receptor in vascular smooth muscle cells. Abbreviations: Ang II, angiotensin II; MAPK, mitogen-activated protein kinase; PAI 1, plasminogen activator inhibitor-1; MCP 1, monocyte chemoattractant protein 1; ICAM 1, intracellular cell adhesion molecule-1; PI3K, inositol 3-phosphatidil kinase; eNOS, endothelial nitric oxide synthase.

Figure 3

Interactions between renin–angiotensin system, kinin–kallikrein system, and insulin signaling transduction pathways. Abbreviations: MAPK, mitogen-activated protein kinase; PI3K, inositol 3 phosphatidil kinase; Ang, Angiotensin; ACE, angiotensin-converting enzyme; ACE2, angiotensin-convert-ing enzyme 2; AT₁, AT₂, angiotensinergic receptors types 1 and 2; Mas, Mas receptor of angiotensin-(1–7); NO, nitric oxide; eNOS, endothelial nitric oxide synthase; ROS, reactive oxygen species; ET1, endothelin 1; TXA₂, thromboxane A₂; PAI 1, plasminogen activator inhibitor; VCMS, vascular smooth muscle cell; ICAM1, intracellular adhesion molecule 1.