Role of aldosterone and angiotensin II in insulin resistance: an update.
The role of the Renin-Angiotensin-Aldosterone system (RAAS) on the development of insulin resistance and cardiovascular disease is an area of growing interest. Most of the deleterious actions of the RAAS on insulin sensitivity appear to be mediated through activation of the Angiotensin II (Ang II) Receptor type 1 (AT(1)R) and increased production of mineralocorticoids. The underlying mechanisms leading to impaired insulin sensitivity remain to be fully elucidated, but involve increased production of reactive oxygen species and oxidative stress. Both experimental and clinical studies also implicate aldosterone in the development of insulin resistance, hypertension, endothelial dysfunction, cardiovascular tissue fibrosis, remodelling, inflammation and oxidative stress. There is abundant evidence linking aldosterone, through non-genomic actions, to defective intracellular insulin signalling, impaired glucose homeostasis and systemic insulin resistance not only in skeletal muscle and liver but also in cardiovascular tissue. Blockade of the different components of the RAAS, in particular Ang II and AT(1)R, results in attenuation of insulin resistance, glucose homeostasis, as well as decreased cardiovascular disease morbidity and mortality. These beneficial effects go beyond to those expected with isolated control of hypertension. This review focuses on the role of Ang II and aldosterone in the pathogenesis of insulin resistance, as well as in clinical relevance of RAAS blockade in the prevention and treatment of the metabolic syndrome and cardiovascular disease.
Lastra-Lastra
Guido
G
Department of Internal Medicine, Division of Endocrinology and Metabolism, Ciudad Universitaria, National University of Colombia School of Medicine, Bogotá, Colombia. lastrag@health.missouri.edu
Sowers
James R
JR
Restrepo-Erazo
Katherine
K
Manrique-Acevedo
Camila
C
Lastra-González
Guido
G
D000450:Aldosterone / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000378:metabolism; D012084:Renin-Angiotensin System
D000804:Angiotensin II; D000450:Aldosterone