Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue
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 concentra...
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doaj-6296d567626b42739fc103046879d1302020-11-25T00:46:41ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-01-011511189120010.3390/ijms15011189ijms15011189Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose TissueMarcus May0Sandor Batkai1Alexander A. Zörner2Dimitrios Tsikas3Jens Jordan4Stefan Engeli5Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyCirculating 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.http://www.mdpi.com/1422-0067/15/1/1189asymmetric dimethylargininenitric oxidenitric oxide synthasedimethylarginine dimethylaminohydrolaseadipose tissuediabetesobesity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marcus May Sandor Batkai Alexander A. Zörner Dimitrios Tsikas Jens Jordan Stefan Engeli |
spellingShingle |
Marcus May Sandor Batkai Alexander A. Zörner Dimitrios Tsikas Jens Jordan Stefan Engeli Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue International Journal of Molecular Sciences asymmetric dimethylarginine nitric oxide nitric oxide synthase dimethylarginine dimethylaminohydrolase adipose tissue diabetes obesity |
author_facet |
Marcus May Sandor Batkai Alexander A. Zörner Dimitrios Tsikas Jens Jordan Stefan Engeli |
author_sort |
Marcus May |
title |
Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue |
title_short |
Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue |
title_full |
Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue |
title_fullStr |
Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue |
title_full_unstemmed |
Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue |
title_sort |
clinical evaluation of extracellular adma concentrations in human blood and adipose tissue |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-01-01 |
description |
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. |
topic |
asymmetric dimethylarginine nitric oxide nitric oxide synthase dimethylarginine dimethylaminohydrolase adipose tissue diabetes obesity |
url |
http://www.mdpi.com/1422-0067/15/1/1189 |
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