Insulin permeability across an in vitro dynamic model of endothelium.
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.
Salvetti
Francesca
F
Departimento di Psichiatria, Neurobiologia, Farmacologia e Biotechnologie, Facoltà di Farmacia, Università degli Studi di Pisa, Italy.
Cecchetti
Paolo
P
Janigro
Damir
D
Lucacchini
Antonio
A
Benzi
Luca
L
Martini
Claudia
C
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
D007328:Insulin