Fig. 1.

Renin–angiotensin system (RAS) and insulin sensitivity. Scheme showing the modulation [by angiotensin AT2 receptor (AT2R) agonist, angiotensin AT1 receptor AT1R blocker (ARB) or angiotensin-converting enzyme (ACE) inhibition] of insulin sensitivity by the RAS and the involvement of pro-/anti-inflammatory signals. The ACE converts angiotensin (Ang) I to Ang II. It also catalyses the degradation of bradykinin (BK), which enhances the expression of glucose transporter type 4 (GLUT4) [29], an effect opposed by AT1R activation [28]. AT1R also disrupts insulin sensitivity by aldosterone-mediated hypokalemia [65], vasoconstriction [5] and inhibition of adipocyte (AC) differentiation [33]. On the other hand, the AT2R promotes AC differentiation via prostacyclin (PGI₂) production [106] and inhibits NF-κB signaling via 11,12-epoxyeicosatrienoic acid (EET) [80], with possible involvement of the peroxisome proliferator-activated receptor-γ (PPAR-γ) [87] vs. [90]. PPAR-γ activation promotes adipocyte differentiation [88] the release of adiponectin with its insulin sensitizing effects [63]