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The renin-angiotensin system and diabetes: an update.

Ribeiro-Oliveira A, Nogueira AI, Pereira RM, Boas WW, Dos Santos RA, Simões e Silva AC - Vasc Health Risk Manag (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Endocrinologia, Departamento de Clínica Médica, Centro Universitário de Belo Horizonte, UNIBH, Belo Horizonte, MG, Brazil.

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.

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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.
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f3-vhrm-4-0787: 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.

Mentions: Besides its NO-dependent effects in the vascular endothelium, insulin also interferes with hemodynamic homeostasis in insulin resistant states (Yki-Jarvinen 2003). In these conditions, insulin can act through MAP-K pathway, promoting cellular growth and other pro-inflammatory and pro-thrombotic actions (Velloso et al 2006). In obese individuals, it has been speculated a possible shift from PI3-K pathway, the molecular via for insulin signal transduction into action, to the MAP-K pathway, offering a molecular explanation by which hyperinsulinemia of these individuals might play a pro-atherogenic role (Hsueh and Quiñones 2003). There is also a possible interaction between insulin and local RAS at this level, since Ang II through AT1 receptors may stimulate the MAP-K pathway and, by doing so, promotes cellular proliferation, inflammation and thrombosis (Velloso et al 2006), while the activation of AT2 receptors could inhibit this same via, meanwhile activating PI3-K (Bedecs et al 1997) (Figure 3). Although a possible antiproliferative action of Ang-(1–7) in this scenario is only speculative, experimental evidence with cardiomyocytes (Tallant et al 2005), pulmonary tumor cells (Gallagher and Tallant 2004), and liver tissue (Pereira et al 2007; Herath et al 2007; Warner et al 2007) corroborates this possibility.


The renin-angiotensin system and diabetes: an update.

Ribeiro-Oliveira A, Nogueira AI, Pereira RM, Boas WW, Dos Santos RA, Simões e Silva AC - Vasc Health Risk Manag (2008)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2597759&req=5

f3-vhrm-4-0787: 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.
Mentions: Besides its NO-dependent effects in the vascular endothelium, insulin also interferes with hemodynamic homeostasis in insulin resistant states (Yki-Jarvinen 2003). In these conditions, insulin can act through MAP-K pathway, promoting cellular growth and other pro-inflammatory and pro-thrombotic actions (Velloso et al 2006). In obese individuals, it has been speculated a possible shift from PI3-K pathway, the molecular via for insulin signal transduction into action, to the MAP-K pathway, offering a molecular explanation by which hyperinsulinemia of these individuals might play a pro-atherogenic role (Hsueh and Quiñones 2003). There is also a possible interaction between insulin and local RAS at this level, since Ang II through AT1 receptors may stimulate the MAP-K pathway and, by doing so, promotes cellular proliferation, inflammation and thrombosis (Velloso et al 2006), while the activation of AT2 receptors could inhibit this same via, meanwhile activating PI3-K (Bedecs et al 1997) (Figure 3). Although a possible antiproliferative action of Ang-(1–7) in this scenario is only speculative, experimental evidence with cardiomyocytes (Tallant et al 2005), pulmonary tumor cells (Gallagher and Tallant 2004), and liver tissue (Pereira et al 2007; Herath et al 2007; Warner et al 2007) corroborates this possibility.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Endocrinologia, Departamento de Clínica Médica, Centro Universitário de Belo Horizonte, UNIBH, Belo Horizonte, MG, Brazil.

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.

Show MeSH
Related in: MedlinePlus