Link between the renin-angiotensin system and insulin resistance: Implications for cardiovascular disease

Ming Sheng Zhou, Ivonne H Schulman, Qiang Zeng

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The incidence of metabolic syndrome is rapidly increasing in the United States and worldwide. The metabolic syndrome is a complex metabolic and vascular disorder that is associated with inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) in the cardiovascular (CV) system and increased CV morbidity and mortality. Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes nitric oxide (NO) production in the endothelium and glucose uptake in insulin-sensitive tissues. Angiotensin (Ang) II inhibits insulin-mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively. On the other hand, Ang II enhances insulin-mediated activation of the mitogen-activated protein kinase (MAPK) pathway, which leads to vasoconstriction and pathologic vascular cellular growth. Therefore, the interaction of Ang II with insulin signaling is fully operative not only in insulin-sensitive tissues but also in CV tissues, thereby linking insulin resistance and CV disease. This notion is further supported by an increasing number of experimental and clinical studies indicating that pharmacological blockade of RAAS improves insulin sensitivity and endothelial function, as well as reduces the incidence of new-onset diabetes in high-risk patients with CV disease. This article reviews experimental and clinical data elucidating the physiological and pathophysiological role of the interaction between insulin and RAAS in the development of insulin resistance as well as CV disease.

Original languageEnglish
Pages (from-to)330-341
Number of pages12
JournalVascular Medicine (United Kingdom)
Volume17
Issue number5
DOIs
StatePublished - Oct 1 2012

Fingerprint

Renin-Angiotensin System
Insulin Resistance
Cardiovascular Diseases
Insulin
Angiotensin II
Phosphatidylinositol 3-Kinase
Blood Vessels
Nitric Oxide
Incidence
Cardiovascular System
Mitogen-Activated Protein Kinases
Vasoconstriction
Endothelium
Pharmacology
Morbidity
Glucose
Mortality
Growth

Keywords

  • angiotensin II
  • cardiovascular disease
  • insulin resistance

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Link between the renin-angiotensin system and insulin resistance : Implications for cardiovascular disease. / Zhou, Ming Sheng; Schulman, Ivonne H; Zeng, Qiang.

In: Vascular Medicine (United Kingdom), Vol. 17, No. 5, 01.10.2012, p. 330-341.

Research output: Contribution to journalArticle

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