The prevalence of Type 2 diabetes mellitus is predicted to increase dramatically over the coming years and the clinical implications and healthcare costs from this disease are overwhelming. In many cases, this pathological condition is linked to a cluster of metabolic disorders, such as obesity, systemic hypertension and dyslipidaemia, defined as the metabolic syndrome. Insulin resistance has been proposed as the key mediator of all of these features and contributes to the associated high cardiovascular morbidity and mortality. Although the molecular mechanisms behind insulin resistance are not completely understood, a negative cross-talk between AngII (angiotensin II) and the insulin signalling pathway has been the focus of great interest in the last decade. Indeed, substantial evidence has shown that anti-hypertensive drugs that block the RAS (renin–angiotensin system) may also act to prevent diabetes. Despite its long history, new components within the RAS continue to be discovered. Among them, Ang-(1–7) [angiotensin-(1–7)] has gained special attention as a counter-regulatory hormone opposing many of the AngII-related deleterious effects. Specifically, we and others have demonstrated that Ang-(1–7) improves the action of insulin and opposes the negative effect that AngII exerts at this level. In the present review, we provide evidence showing that insulin and Ang-(1–7) share a common intracellular signalling pathway. We also address the molecular mechanisms behind the beneficial effects of Ang-(1–7) on AngII-mediated insulin resistance. Finally, we discuss potential therapeutic approaches leading to modulation of the ACE2 (angiotensin-converting enzyme 2)/Ang-(1–7)/Mas receptor axis as a very attractive strategy in the therapy of the metabolic syndrome and diabetes-associated diseases.
Skip Nav Destination
Article navigation
Review Article|
January 14 2014
Modulation of the action of insulin by angiotensin-(1–7)
Fernando P. Dominici;
*IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Correspondence: Dr Fernando P. Dominici (email dominici@qb.ffyb.uba.ar or fernando.dominici@hotmail.com).
Search for other works by this author on:
Valeria Burghi;
Valeria Burghi
*IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for other works by this author on:
Marina C. Muñoz;
Marina C. Muñoz
*IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Search for other works by this author on:
Jorge F. Giani
Jorge F. Giani
†Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 27 2013
Revision Received:
September 27 2013
Accepted:
October 28 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (9): 613–630.
Article history
Received:
June 27 2013
Revision Received:
September 27 2013
Accepted:
October 28 2013
Citation
Fernando P. Dominici, Valeria Burghi, Marina C. Muñoz, Jorge F. Giani; Modulation of the action of insulin by angiotensin-(1–7). Clin Sci (Lond) 1 May 2014; 126 (9): 613–630. doi: https://doi.org/10.1042/CS20130333
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.