title: Insulin permeability across an in vitro dynamic model of endothelium.
abstract: OBJECTIVE
  Endothelium insulin permeability was investigated using in vitro, dynamic culture of endothelial cells.
  
  
  METHODS
  Endothelial cells were cultured in a hollow fiber apparatus and continuously exposed to a flow. Transendothelial electrical resistance and permeability to [14C]sucrose and [14C]inulin were used to monitor the integrity of the endothelial monolayer.
  
  
  RESULTS
  Under these experimental conditions, measurements of insulin permeability, investigated at increasing hormone concentrations, suggested that the predominant transendothelial insulin fluxes were attributable to bidirectional convective transport rather than to a saturable transport mechanism, in agreement with in vivo experiment results published earlier. Analytical determinations of insulin catabolism demonstrated a low percent of insulin degradation by the endothelium, leading to production of insulin metabolites qualitatively identical to those produced by human monocytes.
  
  
  CONCLUSIONS
  The findings of this paper indicated that (a) insulin crosses the endothelial monolayer by paracellular "leak" and endothelial insulin receptors have a minor (if any) role in insulin transport; (b) degradation of the hormone by BAEC is minimal; (c) the in vitro, dynamic culture of endothelial cells presented here should represent a valuable transport model system to study permeability mechanisms of insulin and many other drugs.
authors.affiliation: Departimento di Psichiatria, Neurobiologia, Farmacologia e Biotechnologie, Facoltà di Farmacia, Università degli Studi di Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salvetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Cecchetti
authors.forename: Damir
authors.initials: D
authors.lastname: Janigro
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
authors.forename: Luca
authors.initials: L
authors.lastname: Benzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000493:pharmacokinetics*; D008954:Models, Biological
chemical_list: D007328:Insulin