title: High glucose modulates albumin permeability across glomerular endothelial cells via a protein kinase C-dependent mechanism.
abstract: To investigate the mechanism of glomerular endothelial response to high glucose, an in vitro model of the glomerular endothelial barrier was established in which transfer of fluorescein-labeled albumin across confluent monolayers of immortalized bovine glomerular endothelial cells (GEN) grown on polycarbonate membranes was measured. We first examined the effects of increased concentrations of D-glucose on albumin permeability across GEN monolayers and further investigated the role of protein kinase C (PKC) in the regulation of glucose-induced changes in endothelial barrier function. Incubation with 30 mM D-glucose increased albumin permeability more than those with 10 mM D-glucose. Albumin permeability incubated with 10 mM D-glucose plus 20 mM mannitol was not significantly different from those with 10 mM D-glucose, indicating that the increase in albumin permeability induced by 30 mM D-glucose was not due to high osmolar stimuli. A protein kinase C (PKC) inhibitor, H-7 (25 microM) significantly reduced the permeability-increasing effects of D-glucose. Lactate dehydrogenase release from endothelial cells was not significantly increased above baseline after incubation with 10 mM or 30 mM D-glucose. These results suggest that elevated concentrations of glucose activates PKC, resulting in an increase in albumin permeability across GEN.
authors.affiliation: Department of Medicine, Tokyo Women's Medical College, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nitta
authors.forename: N
authors.initials: N
authors.lastname: Horiba
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: S
authors.initials: S
authors.lastname: Horita
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Kawashima
authors.forename: W
authors.initials: W
authors.lastname: Yumura
authors.forename: H
authors.initials: H
authors.lastname: Nihei
mesh_terms: D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*
chemical_list: D011493:Protein Kinase C; D005947:Glucose