Sex and age-related changes in L-arginine metabolism in peripheral blood leukocytes in young caucasians with type 1 diabetes mellitus

Abstract

We found that hyperactivation of cytoplasmic (anti-inflammatory) and mitochondrial (pro-inflammatory) arginase isoforms in peripheral blood leukocytes (PBL) is more pronounced in women than in male patients with type 1 diabetes mellitus (T1DM) who received insulin for one year, especially in adolescents young adults 15 years old (12.0 - 25.0) compared with children/adolescents 9.3 years old (4.5-11.8). Long-term treatment with insulin up to 14 years (on average 5.3-5.9) reduces the activity of arginase, especially in puberty girls with a tendency to normalize mitochondrial arginase, while in prepubertal boys the activity of both arginase isoforms almost doubles and remains elevated in puberty boys and can be involved in inhibiting nitric oxide synthase (NOS) and decreasing the bioavailability of NO. This is confirmed by the concomitant continuous decrease in the levels of nitric oxide synthase (NOS) products, stable metabolites of NO (nitrite) and L-citrulline in the cytoplasm and mitochondria of PBL in prepubertal girls and boys, in the latter, regardless of age and insulin therapy, while in girls of puberty changes not found, apparently, due to the increased level of sex hormones that promote the expression and activity of NOS, which contribute to the inhibition of arginase. Further studies are needed to understand whether sex and age-related changes found in L-arginine metabolism in PBL can be useful in assessing the stage and progression of T1DM and the effectiveness of therapy.