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Int. J. Mol. Sci. 2014, 15(1), 1189-1200; doi:10.3390/ijms15011189

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

1
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
2
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Received: 10 December 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 17 January 2014
(This article belongs to the Special Issue ADMA and Nitrergic System)
View Full-Text   |   Download PDF [246 KB, 19 June 2014; original version 19 June 2014]   |  

Abstract

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. View Full-Text
Keywords: asymmetric dimethylarginine; nitric oxide; nitric oxide synthase; dimethylarginine dimethylaminohydrolase; adipose tissue; diabetes; obesity asymmetric dimethylarginine; nitric oxide; nitric oxide synthase; dimethylarginine dimethylaminohydrolase; adipose tissue; diabetes; obesity
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

May, M.; Batkai, S.; Zörner, A.A.; Tsikas, D.; Jordan, J.; Engeli, S. Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue. Int. J. Mol. Sci. 2014, 15, 1189-1200.

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