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.

中文翻译：

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与1型糖尿病的年轻白种人的外周血白细胞L-精氨酸代谢相关的性别和年龄变化

我们发现，女性的外周血白细胞（PBL）细胞质（抗炎）和线粒体（促炎）精氨酸酶同种型的过度激活比接受胰岛素治疗一年的男性1型糖尿病（T1DM）患者更为明显。 ，尤其是15岁（12.0-25.0）的青少年，而9.3岁（4.5-11.8）的儿童/青少年。长期使用胰岛素治疗长达14年（平均5.3-5.9）会降低精氨酸酶的活性，尤其是在青春期女孩中，线粒体精氨酸酶趋于正常，而青春期前男孩中两种精氨酸酶同工酶的活性几乎翻倍并保持升高在青春期男孩中可能参与抑制一氧化氮合酶（NOS）并降低NO的生物利用度。不论青春期前的男女生中，一氧化氮合酶（NOS）产物水平，PBL的细胞质和线粒体中一氧化氮合酶（NOS）和L-瓜氨酸的稳定代谢产物的水平持续降低，证实了这一点。年龄和胰岛素疗法虽然在青春期女孩中并未发现变化，但显然是由于促进NOS表达和活性的性激素水平增加，这有助于精氨酸酶的抑制。需要进一步的研究来了解PBL中L-精氨酸代谢中发现的性别和年龄相关变化是否可用于评估T1DM的阶段和进展以及治疗的有效性。在青春期前的男女生中，PBL的胞质和线粒体中NO（亚硝酸盐）和L-瓜氨酸的稳定代谢产物，无论年龄和胰岛素治疗，在后者中均未发现变化，显然是由于青春期女孩的增加促进NOS表达和活性的性激素水平，有助于抑制精氨酸酶。需要进一步的研究来了解PBL中L-精氨酸代谢中发现的性别和年龄相关变化是否可用于评估T1DM的阶段和进展以及治疗的有效性。在青春期前的男女生中，PBL的胞质和线粒体中NO（亚硝酸盐）和L-瓜氨酸的稳定代谢产物，无论年龄和胰岛素治疗，在后者中均未发现变化，显然是由于青春期女孩的增加促进NOS表达和活性的性激素水平，有助于抑制精氨酸酶。需要进一步的研究来了解PBL中L-精氨酸代谢中发现的性别和年龄相关变化是否可用于评估T1DM的阶段和进展以及治疗的有效性。