Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia

Eid, H.M.A.; Reims, Henrik M.; Arnesen, Harald; Kjeldsen, Sverre E.; Lyberg, Torstein; Seljeflot, Ingebjørg

doi:10.1016/j.metabol.2006.11.003

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…Furthermore, they found that in patients with type 2 diabetes mellitus, low plasma ADMA levels were independently correlated with poor glycemic control and increased GFR. 41 Eid et al 42 have recently shown that infusion of insulin during glucose clamping is accompanied by a significant reduction in circulating ADMA levels. Similarly, in experimental studies, the accumulation of ADMA in human endothelial cells was markedly inhibited by increasing doses of insulin.…”

Section: Discussionmentioning

confidence: 99%

Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study

et al. 2007

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Background-Elevated asymmetrical dimethylarginine (ADMA) is a novel risk factor for atherosclerosis that may impair endothelial function by interfering with endothelial nitric oxide synthesis. To gain insight into the effects of ADMA on systemic endothelial function, we examined the association between ADMA and brachial artery flow-mediated dilation (FMD) in a large population of young adults. Methods and Results-Plasma ADMA and brachial FMD, as well as conventional cardiovascular risk factors, were measured in 2096 white adults aged 24 to 39 years. In univariate analysis, ADMA was inversely correlated with FMD (rϭϪ0.07, Pϭ0.003). The inverse association between ADMA and FMD remained significant in a multivariable regression model adjusted for age, sex, conventional cardiovascular risk factors, estimated glomerular filtration rate, and brachial artery baseline diameter (␤ϮSE Ϫ1.56Ϯ0.62%, Pϭ0.01). Conclusions-We conclude that elevated plasma ADMA concentrations are associated with decreased brachial FMD responses in healthy adults. These data provide evidence at the population level that ADMA levels are associated with endothelial function.

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Section: Discussionmentioning

confidence: 99%

Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study

et al. 2007

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“…24 Other explanations include reduced protein catabolism and increased uptake of ADMA into cells through up-regulation of the cationic amino acid transporter. 109 It has already been stated that excessive NO production can be harmful, and has been implicated in the development of septic shock. 110 Because of this, inhibition of iNOS with MMA was advanced as a possible way of reducing mortality.…”

Section: Adma In Critical Illnessmentioning

confidence: 99%

The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine

Blackwell

2009

Ann Clin Biochem

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Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and an important cause of endothelial dysfunction. Its increased plasma concentration is associated with a variety of traditional cardiovascular risk factors, and may mediate their effects on the vascular endothelium. ADMA is also an independent predictor of cardiovascular events and mortality, and predicts outcomes in critically ill patients in the intensive care unit. This work has provided insights into the role of ADMA as an endogenous regulator of nitric oxide synthesis. At present there is no specific therapy to modify ADMA concentration, but increasing interest and work on protein arginine methyltransferases and dimethylarginine dimethylaminohydrolase, which synthesize and metabolize ADMA, respectively, might provide novel therapeutic targets.

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“…Admittedly, the percentage of insulin users was higher, albeit not significantly, in patients receiving metformin. However, keeping in mind the ability of insulin to lower ADMA levels in humans (Siroen et al 2005;Eid et al 2007), this effect would rather decrease, not increase ADMA concentrations, whereas ADMA was higher in the study subjects on metformin. Finally, the observed differences were maintained after limitation of the analysis to patients receiving only oral antidiabetic drugs.…”

Section: Discussionmentioning

confidence: 98%

“…Additionally, ADMA levels were reportedly elevated (Abbasi et al 2001;Konukoglu et al 2008), similar (Böger et al 2009) and even decreased (Päivä et al 2003) in individuals with T2DM compared to controls without diabetes. This discrepancy was linked to a complex interplay of various factors (Teerlink et al 2009;Anderssohn et al 2010), including on the one side the hyperglycemia-induced inhibition of the major ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) (Lin et al 2002) and positive effects of insulin resistance by itself (Stühlinger et al 2002;Marliss et al 2006) on ADMA concentrations, and-on the other side-negative modulation of circulating ADMA by glomerular hyperfiltration at an initial stage of diabetic nephropathy (Päivä et al 2003) and probably by the hyperinsulinemia-dependent potentiation of ADMA influx into the cells (Siroen et al 2005;Eid et al 2007). Moreover, relations between glucose metabolism and the l-arginine-NO pathway appear bidirectional because NO is able to influence insulin secretion, action and clearance (Kruszelnicka 2014).…”

Section: Introductionmentioning

confidence: 99%

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

et al. 2015

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Metformin, the drug of first choice in type 2 diabetes mellitus (T2DM), reduces cardiovascular (CV) morbidity and mortality in part independently of improved glycemic control and changes in traditional risk factors. However, there are discordant reports on the effects of metformin on endothelial function in T2DM. Our aim was to compare biochemical endothelial markers in patients with stable coronary artery disease (CAD) and T2DM stratified by metformin use. We studied 70 patients (29 women, age 68 ± 9 years) with established T2DM referred for elective coronary angiography owing to stable angina who were receiving a standard CV medication and metformin or other oral antidiabetic drugs. Exclusion criteria included heart failure and other relevant coexistent disorders. Biochemical indices of endothelial dysfunction and activation at admission were compared according to metformin use for at least 1 year prior to index hospitalization. Clinical characteristics were similar in patients receiving metformin (n = 40) vs. those on other oral antidiabetic agents (n = 30). Plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) was lower (553 ± 148 vs. 668 ± 170 µg/L, P = 0.004) and asymmetric dimethylarginine (ADMA) higher (0.53 ± 0.09 vs. 0.48 ± 0.08 µM, P = 0.01) in subjects on metformin, which was maintained in multivariate analysis. Symmetric dimethylarginine, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and E-selectin did not differ across the groups. The results were substantially unchanged after exclusion of insulin users. Thus, metformin use appears differentially associated with sVCAM-1 and ADMA in patients with T2DM and stable CAD. Whether this observation may reflect different prognostic effects of these endothelial markers in diabetes remains to be studied.

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Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia

Cited by 35 publications

References 39 publications

Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study

Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study

The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

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