title: Effect of mild hyperisulinemia on conduit vessel endothelial function:  role of noradrenergic activation.
abstract: OBJECTIVE
  The evidence that an exogenously induced modest hyperinsulinemia deteriorates conductance artery endothelial function - flow-mediated dilatation (FMD) - in healthy individuals is in contrast with in-vitro and in-vivo studies that consistently found that insulin facilitates both nitric oxide release and the endothelium-dependent dilatation. The aim of this study was to verify whether this effect is caused by the enhancement of insulin-induced adrenergic tone.
  
  
  METHODS
  In 10 healthy male volunteers, endothelium-dependent (FMD) and endothelium-independent (glyceryl trinitrate, GTN) dilatation were evaluated by high-resolution ultrasound of the brachial artery, combined with a computerized edge detection system, at baseline (-60 and 0 min) and after 120 and 240 min during insulin infusion (INS study). In five participants, randomly selected from the initial group, the study was repeated during an isotonic saline (0.9% sodium chloride) intravenous infusion (SAL study). In an additional five participants, insulin infusion was preceded by an intravenous infusion of clonidine started 40 min before insulin and continued throughout the study (INS + CLN study).
  
  
  RESULTS
  Plasma norepinephrine concentration increased in the INS study from 260 ± 40 to 333 ± 62 pg/ml (P < 0.05), whereas it remained stable throughout the INS + CLN study. In the INS study, no change in FMD was observed, whereas the response to GTN tended to decrease (P = 0.09). In the INS + CLN study, no significant changes in FMD response were observed, whereas GTN response was completely restored.
  
  
  CONCLUSIONS
  Physiological hyperinsulinemia has no effect on endothelium-dependent vasodilatation in conduit vessels of healthy individuals, but it induces a slight decline in endothelium-independent vasodilatation, which is entirely explained by the insulin-induced noradrenergic activation.
authors.affiliation: Metabolism and Hypertension Units, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.forename: Francesco
authors.initials: F
authors.lastname: Stea
authors.forename: Beatrice
authors.initials: B
authors.lastname: Boldrini
authors.forename: Emiliano
authors.initials: E
authors.lastname: Duranti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000097:blood*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D012039:Regional Blood Flow / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
chemical_list: D000316:Adrenergic alpha-Agonists; D007328:Insulin; D012965:Sodium Chloride; D005996:Nitroglycerin; D009638:Norepinephrine