Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue

International Journal of Molecular Sciences

Marcus May²  Sandor Batkai¹  Alexander A. Zörner²  Dimitrios Tsikas²  Jens Jordan² 

[1]Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany

[2] E-Mail:

[3]Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany

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关键词: asymmetric dimethylarginine;    nitric oxide;    nitric oxide synthase;    dimethylarginine dimethylaminohydrolase;    adipose tissue;    diabetes;    obesity;   

DOI  :  10.3390/ijms15011189

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland