title: The microvascular response to transdermal iontophoresis of insulin is mediated by nitric oxide.
abstract: OBJECTIVE
  Insulin has direct effects on blood flow in various tissues, most likely due to endothelial NO production. We investigated whether insulin delivered to the skin by iontophoresis increases microvascular perfusion and whether this effect is partly or completely mediated by the release of NO.
  
  
  METHODS
  In healthy subjects, regular insulin and monomeric insulin were delivered to the skin by cathodal iontophoresis. The skin was pretreated either with L-NAME or control solution (PBS) using anodal iontophoresis. Microvascular responses were measured using laser Doppler flowmetry.
  
  
  RESULTS
  A dose-dependent increase in perfusion was observed during iontophoresis of regular and monomeric insulin. The maximum perfusion was significantly elevated compared with control after PBS (regular insulin 53.6 (12.7-95.6) PU vs. 4.2 (3.4-4.8) PU, p = 0.002; monomeric insulin 32.6 (8.9-92.6) PU vs. 5.9 (3.4-56.0) PU, p = 0.03). The microvascular response to insulin was abolished after L-NAME (regular insulin: 25.6 (11.6-54.4) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.15; monomeric insulin 10.9 (5.4-56.8) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.22).
  
  
  CONCLUSIONS
  The main finding is that iontophoresis of insulin induces a dose-dependent vasodilation in the skin, which could be suppressed after pretreatment with a NO synthase inhibitor. This suggests that vasodilation in the skin after iontophoresis of insulin is mediated by the NO pathway.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Iredahl
authors.forename: Erik
authors.initials: E
authors.lastname: Tesselaar
authors.forename: Saikat
authors.initials: S
authors.lastname: Sarker
authors.forename: Simon
authors.initials: S
authors.lastname: Farnebo
authors.forename: Folke
authors.initials: F
authors.lastname: Sjöberg
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007478:Iontophoresis; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester
keywords: endothelial function; insulin; transdermal iontophoresis; vasodilation