Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia.
Endothelial dysfunction is reflected by an impaired nitric oxide (NO)-mediated vasodilatation. Insulin resistance may be linked to endothelial dysfunction by several mechanisms, including disturbances in signaling pathways common to both insulin action and NO production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may contribute to endothelial dysfunction, and elevated ADMA levels have been associated with both insulin levels and the degree of insulin resistance. The direct link between insulin and ADMA, however, has not yet been established. In the present study, we aimed to investigate the effects of acute hyperinsulinemia on circulating ADMA and L-arginine levels and on forearm blood flow (FBF). Male volunteers, aged 21 to 24 years, with borderline hypertension were included in the study. The participants underwent a 90-minute hyperinsulinemic isoglycemic glucose clamp with insulin levels at the postprandial levels (n=20) or a saline infusion (control) (n=9). Fasting blood samples were drawn at baseline and after 90 minutes. Insulin infusion was accompanied by a reduction in ADMA (0.78 to 0.68 micromol/L, P<.01), which was significantly different (P=.001) from the increase seen in the saline control group (0.69 to 0.79 micromol/L, P<.05). The same profile was obtained for L-arginine with a significantly more pronounced decrease (P<.001) in the insulin clamp group (74 to 61 micromol/L, P<.001) than in the saline control group (59 to 57 micromol/L, P=.95). The FBF level and nitrate/nitrite (NOx) levels were not affected by any of the clamp procedures. Short-term administration of insulin was accompanied by a decrease in both ADMA and L-arginine levels, with no change in FBF, in our population of young men with borderline hypertension. The possible influence of insulin on ADMA levels in a chronic state of insulin resistance can, however, not be deduced from the present investigation.
Eid
Hilde Marie Angell
HM
Center for Clinical Research, Department of Cardiology, Ullevaal University Hospital, Oslo, Norway. h.m.eid@medisin.uio.no
Reims
Henrik
H
Arnesen
Harald
H
Kjeldsen
Sverre Erik
SE
Lyberg
Torstein
T
Seljeflot
Ingebjørg
I
D000208:Acute Disease; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D010991:Plethysmography
D007328:Insulin; C487735:dimethylarginine; D001120:Arginine