Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Int J Mol Sci. 2014 Jan 17;15(1):1189-200. doi: 10.3390/ijms15011189.
Circulating asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, has been proposed as a biomarker for clinical outcome. Dimethylarginine dimethylaminohydrolase (DDAH) is the main enzyme responsible for ADMA metabolism and elimination. Adipose tissue ADMA concentrations and DDAH activity and their role in diabetes and obesity have not yet been investigated. In this study, we evaluated clinical microdialysis in combination with a sensitive analytical method (GC-MS/MS) to measure ADMA concentrations in extracellular fluid. Adipose tissue ADMA concentrations were assessed before and during an oral glucose tolerance test in lean healthy subjects and subjects with diabetes (n = 4 each), and in morbidly obese subjects before and after weight loss of 30 kg (n = 7). DDAH activity was determined in subcutaneous and visceral adipose tissue obtained during laparoscopic surgery (n = 5 paired samples). Mean interstitial ADMA concentrations did not differ between study populations (healthy 0.17 ± 0.03 µM; diabetic 0.21 ± 0.03 µM; morbidly obese 0.16 ± 0.01 and 0.17 ± 0.01 µM before and after weight loss, respectively). We did not observe any response of interstitial ADMA concentrations to the oral glucose challenge. Adipose tissue DDAH activity was negligible compared to liver tissue. Thus, adipose tissue ADMA plays a minor role in NO-dependent regulation of adipose tissue blood flow and metabolism.
循环不对称二甲基精氨酸 (ADMA)，一种内源性一氧化氮合成抑制剂，被提议作为临床结果的生物标志物。二甲基精氨酸二甲氨基水解酶 (DDAH) 是负责 ADMA 代谢和消除的主要酶。脂肪组织 ADMA 浓度和 DDAH 活性及其在糖尿病和肥胖中的作用尚未得到研究。在这项研究中，我们评估了临床微透析与灵敏分析方法（GC-MS/MS）相结合，以测量细胞外液中的 ADMA 浓度。在健康的瘦人和糖尿病患者（每组 4 人）进行口服葡萄糖耐量试验之前和期间评估了脂肪组织 ADMA 浓度，并在病态肥胖患者进行了 30 公斤体重减轻之前和之后评估了 ADMA 浓度（n = 7）。在腹腔镜手术期间（n = 5 对样本）确定了皮下和内脏脂肪组织中的 DDAH 活性。间质 ADMA 浓度在研究人群之间没有差异（健康组 0.17 ± 0.03 µM；糖尿病组 0.21 ± 0.03 µM；病态肥胖组分别在体重减轻前和体重减轻后为 0.16 ± 0.01 和 0.17 ± 0.01 µM）。我们没有观察到间质 ADMA 浓度对口服葡萄糖挑战有任何反应。与肝组织相比，脂肪组织 DDAH 活性可以忽略不计。因此，脂肪组织 ADMA 在 NO 依赖性调节脂肪组织血流和代谢中起次要作用。
