title: Effect of insulin on human aortic endothelial nitric oxide synthase.
abstract: 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.
authors.affiliation: Division of Endocrinology, State University of New York at Buffalo and Kaleida Health, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Aljada
authors.forename: P
authors.initials: P
authors.lastname: Dandona
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D013268:Stimulation, Chemical; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D014680:Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III