Asymmetric dimethylarginine: A molecule responsible for the coexistence of insulin resistance and atherosclerosis via dual nitric oxide synthase inhibition
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- 作者：Judit Zsuga ; Rudolf Gesztelyi ; Já ; nos Tö ; rö ; k ; Sá ; ndor Ké ; ki ; Dá ; niel Bereczki
- 关键词：Autism ; Autism spectrum disorders ; Spironolactone ; Androgen ; Testosterone ; Neuroglia ; Neuroinflammation ; Inflammation ; Immune dysregulation ; Anti-inflammatory ; Anti-androgen
- 刊名：Medical Hypotheses
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：65
- 期：6
- 页码：1091-1098
- 全文大小：136 K
文摘
Asymmetric dimethylarginine (ADMA) has been recently identified as the major endogenous inhibitor of soluble nitric oxide synthase. Its systemic accumulation was observed in conjunction with atherosclerosis and several cardiovascular and metabolic diseases. Here, we propose that ADMA causes insulin resistance by the inhibition of the neuronal isoform of nitric oxide synthase, while the simultaneously observed atherosclerosis is the consequence of endothelial nitric oxide synthase (NOS) inhibition. Our hypothesis rests on animal models in which experimental insulin resistance was induced by intraportal administration of non-selective and selective neuronal nitric oxide synthase inhibitors, N-methyl-l-arginine (l-NMMA) or 7-nitroindazole. In these models, loss of hepatic nitric oxide productions is presumed to hinder a very potent insulin sensitizing mechanism referred to as meal induced sensitization that is anatomically linked to the nitrergic fibers of the anterior hepatic plexus. Cause and effect relationship between ADMA and insulin resistance has been proposed previously by others however the nature of this relationship has not been elucidated in detail. In our hypothesis, we suggest that ADMA by inhibiting both the neuronal and the endothelial forms of NOS, results both in insulin resistance and in accelerated atherosclerosis, therefore ADMA is the molecule responsible for the coexistence of these two conditions. We also suggest animal models and human studies to test our hypothesis, the results of which may offer novel approaches in the prevention of insulin resistance and atherosclerosis.