Effect of insulin on human aortic endothelial nitric oxide synthase

Metabolism. 2000 Feb;49(2):147-50. doi: 10.1016/s0026-0495(00)91039-4.


It has recently been shown that insulin induces vasodilation in human arteries and veins in vivo. This effect of insulin has been shown to be a direct one on the human vein. In view of these observations and the fact that insulin-induced vasodilation is impaired in insulin-resistant states like type 2 diabetes and obesity, we have investigated the hypothesis that insulin may induce the expression of endothelial nitric oxide synthase (e-NOS) in endothelial cells grown from human aortae (HAECs), human lower-limb veins, and human umbilical veins (HUVECs), and microvascular endothelial cells (MVECs) from human adipose tissue. The expression of e-NOS was maximal in HAECs, and therefore, further experiments were performed on these cells. When cells reached 90% confluence, they were induced with different concentrations of insulin (0, 25, 100, and 1,000 microU/mL) for 6 days. The cells were homogenized and e-NOS expression was examined by Western blotting. A dose-dependent induction by insulin of e-NOS in the endothelial cells was clearly demonstrated. There was no detectable level of the inducible NOS isoform (i-NOS), and this effect of insulin was independent of cell proliferation. We conclude that insulin induces a dose-dependent induction of e-NOS in human aortic cells (and possibly arterial/endothelial cells), and this effect may contribute to the overall vasodilatory effect of insulin.

MeSH terms

  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / enzymology*
  • Arteries / cytology
  • Arteries / drug effects
  • Arteries / enzymology
  • Blotting, Western
  • Cell Division / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Immunohistochemistry
  • Insulin / pharmacology*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Stimulation, Chemical
  • Time Factors
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Veins / cytology
  • Veins / drug effects


  • Hypoglycemic Agents
  • Insulin
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III