Role of aldosterone and angiotensin II in insulin resistance: an update
Abstract
Summary: 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.
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The renin-angiotensin-aldosterone system induces insulin resistance on local and systemic levels, which explains why therapies that interfere with the RAAS reduce the incidence of type 2 diabetes mellitus.
“Apart from its major function of sodium and water retention, the RAAS was found to induce insulin resistance on local and systemic levels, which explains why therapies that interfere with the RAAS reduce the incidence of type 2 diabetes mellitus [71-73].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [72]
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“It seems that hormones of the RAAS exert these effects via intracellular induction of reactive oxygen species [71,72].”
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- Authors
- Lastra‐Lastra, G., Sowers, J. R., Restrepo‐Erazo, K., Manrique‐Acevedo, C., & Lastra‐González, G.
- Affiliations
- Universidad Nacional de Colombia (CO)
- University of Missouri (US)
- Corresponding author
- Lastra‐González, Guido
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2009-06-10
- Volume
- 71
- Issue
- 1
- Pages
- 1-6
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2094842922
- Cited by
- 90
- References
- 51
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 11 · 2013: 7 · 2012: 11
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- aldosterone, angiotensin II, insulin resistance, renin-angiotensin-aldosterone system, angiotensin II type 1 receptor, mineralocorticoids, oxidative stress, insulin signaling, glucose homeostasis, cardiovascular disease, metabolic syndrome, RAAS blockade, endothelial dysfunction, hypertension, fibrosis
- MeSH terms
- Aldosterone, Angiotensin II, Animals, Cardiovascular Diseases, Humans, Insulin Resistance, Metabolic Diseases, Renin-Angiotensin System
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