Purpose. 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 [C-14]sucrose and [C-14]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.

Insulin permeability across an in vitro dynamic model of endothelium

LUCACCHINI, ANTONIO;BENZI, LUCA;MARTINI, CLAUDIA
2002

Abstract

Purpose. 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 [C-14]sucrose and [C-14]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, F; Cecchetti, P; Janigro, D; Lucacchini, Antonio; Benzi, Luca; Martini, Claudia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/204328
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