Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm.
Insulin-mediated vasodilation has been proposed as an important determinant of whole-body insulin-stimulated glucose disposal. However, it is not clear whether the vasodilator effect of insulin results from a direct action of the hormone or whether alternative mechanisms are involved. To better characterize the mechanism of insulin-mediated vasorelaxation, we compared forearm blood flow (FBF) responses to local (intra-arterial) and systemic (intravenous, euglycemic clamp) hyperinsulinemia in 10 healthy lean subjects using venous occlusion plethysmography. In addition, we assessed the effect of nitric oxide (NO) synthase inhibition by NG-monomethyl-L-arginine (L-NMMA) on the vasodilator and metabolic responses to hyperinsulinemia. Similar forearm concentrations of insulin were achieved during local and systemic infusion (231+/-39 versus 265+/-22 microU/mL; P=0.54). Of note, FBF did not change significantly in response to local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/-0.3 mL . min-1 . dL-1; P=0.50). In contrast, systemic hyperinsulinemia caused a 52% increase in FBF (from 2.5+/-0.2 to 3. 8+/-0.5 mL . min-1 . dL-1; P<0.004), which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min-1 . dL-1; P=0. 004). We conclude that systemic, but not local, hyperinsulinemia induces vasodilation in the forearm. Our findings suggest that insulin-mediated vasodilation is not due solely to a direct stimulatory effect of insulin but involves additional mechanisms activated only during systemic hyperinsulinemia.
Cardiology Branch, Hypertension-Endocrine Branch, National Heart, Lung,and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
C
C
Cardillo
C M
CM
Kilcoyne
S S
SS
Nambi
R O
RO
Cannon
M J
MJ
Quon
J A
JA
Panza
D005260:Female; D005542:Forearm; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D006439:Hemodynamics; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D007328:Insulin; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D005947:Glucose