Role of the angiotensin type 2 receptor on insulin sensitivity and action.

MUÑOZ MC; CAROLINA GIL; QUIROGA DT; DOMINICI FP

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad de Investigación Clínica; 2018

Introduction. The renin-angiotensin system is a hormonal cascade that controls important physiological functions through the actions of angiotensin II (Ang II) which acts through two types of receptors, the Ang II type 1 receptor (AT1R) and the Ang II type 2 receptor (AT2R). The AT1R mediates the main physiological effects of Ang II. Chronic elevation of Ang II interferes negatively with the metabolic actions of insulin. Treatment with AT1R antagonists improves this condition. In contrast, little is know about the role of the AT2R on the modulation of insulin actions. The evidence obtained by the stimulation or antagonism of the AT2R, indicates that the AT2R is involved in the glucose homeostasis, but the information obtained so far using AT2RKO mice is not consistent.Objective. To analyze the impact of the global elimination of the AT2R on glucose homeostasis. It is postulated that the elimination of the AT2R will generate a reduction of insulin sensitivity.Methods. Male and female AT2KO mice (4 months), were provided by Dr. Pedro Miguel Geraldes, University of Sheerbroke, Montreal, Canada. We evaluated the effect of the absence of the AT2R on insulin sensitivity (insulin tolerance test), glucose tolerance (glucose tolerance test) and circulating metabolic parameters. The in vivo status of main components of the insulin pathway was analyzed by western blotting.Results. Female AT2KO mice showed a reduction in insulin sensitivity while males did not present differences when compared to their respective controls. Female AT2KO mice displayed a reduction in the insulin-stimulated phosphorylation of both the insulin receptor and Akt at activating residues in white adipose tissue compared with respective controls.Conclusions. Our findings show that female AT2RKO mice display decreased insulin sensitivity, associated with a reduction in the response to insulin at the phosphorylation of the insulin receptor and Akt in adipose tissue.