Over the last decades, angiotensin II (AngII) has played an important role in the pathophysiology of metabolic disorders such as obesity, insulin resistance and type 2 diabetes. It was shown that AngII contributes significantly to the recruitment of splenic monocytes for myocardial infarct. However, the direct role of AngII systemic elevation in the infiltration of monocytes/macrophages from the spleen into adipose tissue and its implications in the genesis of obesity and insulin resistance is not clear. The objective of the present study was to evaluate the role of AngII in the splenic monocytes/macrophages output and the induction of insulin resistance in mice.


Swiss mice were kept in controlled environment and had access to water and food ad libitum. One group received AngII injections (10 and 1000 μg/kg/day for 2 days, and the other group received AngII infusion with a subcutaneous infusion pump for 14 days (0.25 μl/h at 100 ng/kg/day). Part of both groups received losartan (30 mg/kg/day) concomitantly following the treatment period. Insulin and glucose tolerance test were performed. Additionally, monocytes and macrophages were quantified in the spleen and blood by flow cytometry.


Acute injection of AngII, at a concentration of 1 mg/kg/day, but not at a concentration of 10 μg/kg/day, was able to reduce insulin tolerance. On the other hand, none of the acutely administered doses were able to alter the number of splenic monocytes/macrophages. Chronic infusion of AngII significantly reduced the insulin sensitivity and glucose tolerance. Additionally, the chronic infusion of Ang II reduced the number of Ly6Chi monocytes in the spleen, indicating that this cell population is mobilized by systemic increase of AngII.


These results suggest that a chronic increase of AngII might be involved in the recruitment of splenic monocytes of pro-inflammatory profile, which seems to contribute to the development of insulin resistance in mice.