Effect of supplemental L-arginine on the function of T lymphocytes and the formation of advanced glycosylated end products in rats with streptozotocin-induced diabetes

Objective: We investigated the effect of supplemental l-arginine on lymphocyte function in diabetes and its association with suppressed formation of advanced glycosylated end products (AGEs). Methods: For the in vivo study, rats with streptozotocin-induced (65 mg/kg of body weight, intravenously) diabetes were treated with or without 2% l-arginine or glycine (as a positive control) in drinking water for 8 wk. We then measured serum fructosamine concentrations and concanavalin A-induced proliferative ability of lymphocytes from these animals. For the in vitro study, AGEs derived from albumin were prepared by incubating d-glucose (200 mmol/L) and bovine serum albumin (100 mg/mL) at 37°C for 2 wk in the presence or absence of l-arginine (0.1-10 mmol/L). These preparations were quantified for their bovine serum albumin - derived AGE content, and their effect on concanavalin A-induced proliferative activity of T lymphocyte from normal rats was measured. Results: Serum fructosamine concentrations were significantly higher in the diabetic rats than in the control rats (P < 0.05) but were significantly lowered with l-arginine supplementation (P < 0.05). The lower lymphocyte proliferation rate found in the diabetic rats was reversed by supplemental l-arginine (P < 0.05). During the course of incubation of bovine serum albumin with d-glucose, the presence of l-arginine prevented the formation of bovine serum albumin-derived AGEs and attenuated their inhibitory effect on the rate of lymphocyte proliferation in a dose-dependent manner. Conclusion: Supplemental l-arginine improved the function of T lymphocytes in diabetic rats in association with decreased formation of AGEs.