Metabolic Role of Angiotensin-(1-7)/Mas Axis

DOMINICI FP; SANTOS SH

The Protective Arm of the Renin Angiotensin System (RAS).Functional Aspects and Therapeutic Implications.

ELSEVIER SCIENCE BV

Año: 2015; p. 249 - 254

The renin?angiotensin system (RAS) is initiated by the expression of angiotensinogen (AGT) at different tissues and cells including hepatocytes, myocytes, and adipocytes. However, the liver is regarded as the primary source of AGT in the nondiseased state. Renin enzyme cleaves AGT to produce Ang I, a peptide that is rapidly hydrolyzed by the angiotensin converting enzyme (ACE) to the octapeptide, Ang II. Besides Ang II, several other angiotensin peptides formed from AGT have biological activity; nevertheless, the main one is Ang-(1-7), which broadly opposes Ang II actions. Ang-(1-7) can also be produced as a product from the degradation of Ang II through the action of the ACE homologue enzyme, the so-called ACE2. Ang-(1-7) and Ang II have been implicated in insulin resistance and associated with metabolic syndrome, within antagonistic actions. Previous studies demonstrated that Ang II by acting through type 1 (AT1) receptors produces endothelial dysfunction and metabolic changes leading to hypertension and metabolic syndrome.18 More recent studies have demonstrated that Ang-(1-7) by acting at the Mas receptor opposes several metabolic effects of Ang II, which in turn improves insulin sensitivity, glucose tolerance, and type 2 diabetes; reduces body fat; increases adiponectin production; and reverses hyperleptinemia. Indeed, Ang-(1-7) decreases the release of inflammatory mediators by the adipose tissue in obese animal models, (Figure 1). More recently, Andrade et al. demonstrated that Ang-(1-7) modulates sirtuins (enzymes that regulate metabolism) and improves type 2 diabetes. Besides, Muñoz et al. showed that the Mas receptor is an essential component of the insulin receptor signaling pathway. Taken together, all these facts indicate that blunting Ang II actions and stimulating Ang-(1-7) signaling appears an attractive therapeutic approach for chronic metabolic disorders.