L-arginine catabolism is driven mainly towards nitric oxide synthesis in the erythrocytes of patients with type 2 diabetes at first clinical onset

Abstract

Background: We investigated the l-arginine (l-Arg)-nitric oxide (NO) metabolic pathway in the erythrocytes (RBCs) and plasma of subjects with type 2 diabetes at first clinical onset.

Methods: RBCs and plasma were collected from 26 patients with type 2 diabetes at first clinical onset and 19 age-matched non-diabetes subjects as controls. l-Arg content was assayed by capillary electrophoresis. We measured arginase activity and nitrate/nitrite concentrations by spectrophotometry, and glycosylated haemoglobin (HbA1c) by standardized immunoturbidimetry.

Results: We found that, when compared with controls, l-Arg content was similar in RBCs while decreased in the plasma of patients with type 2 diabetes. Interestingly, arginase activity was lower in RBCs and increased in plasma of patients with diabetes. NO production was higher in RBCs in patients with type 2 diabetes, while no difference was found in the plasma of our subjects.

Conclusions: l-Arg catabolism is driven mainly towards NO synthesis in RBCs of patients with type 2 diabetes at first clinical onset. The decreased RBC arginase activity could be considered a potential mechanism of increased RBC NO production in early diabetes. Therefore, the RBC pool would represent a potentially compensatory intravascular compartment for endothelial dysfunction in diabetes.

Keywords: l-arginine; nitric oxide; type 2 diabetes.