Therapeutic Opportunities in Targeting the Protective Arm of the Renin-angiotensin System to Improve Insulin Sensitivity: a Mechanistic Review

Overview

Journal Hypertens Res

Specialty Cardiology & Vascular Diseases

Date 2024 Oct 3

PMID 39363004

Authors

Fernando P Dominici

Mariela M Gironacci

Jorge A Narvaez Pardo

Affiliations

Soon will be listed here.

Abstract

In recent years, the knowledge of the physiological and pathophysiological roles of the renin-angiotensin system (RAS) in glucose metabolism has advanced significantly. It is now well-established that blockade of the angiotensin AT receptor (ATR) improves insulin sensitivity. Activation of the AT receptor (ATR) and the MAS receptor are significant contributors to this beneficial effect. Elevated availability of angiotensin (Ang) II) for interaction with the ATR and increased Ang-(1-7) formation during ATR blockade mediate these effects. The ongoing development of selective ATR agonists, such as compound 21 and the novel Ang III peptidomimetics, has significantly advanced the exploration of the role of ATR in metabolism and its potential as a therapeutic target. These agents show promise, particularly when RAS inhibition is contraindicated. Additionally, other RAS peptides, including Ang IV, des-Asp-Ang I, Ang-(1-9), and alamandine, hold therapeutic capability for addressing metabolic disturbances linked to type 2 diabetes. The possibility of ATR heteromerization with either ATR or MAS receptor offers an exciting area for future research, particularly concerning therapeutic strategies to improve glycemic control. This review focuses on therapeutic opportunities to improve insulin sensitivity, taking advantage of the protective arm of the RAS.

Citing Articles

Angiotensin-(1-7) and Central Control of Cardiometabolic Outcomes: Implications for Obesity Hypertension.

Vernail V, Lucas L, Miller A, Arnold A Int J Mol Sci. 2025; 25(24.

PMID: 39769086 PMC: 11677932. DOI: 10.3390/ijms252413320.

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