title: Mice lacking insulin or insulin-like growth factor 1 receptors in vascular endothelial cells maintain normal blood-brain barrier.
abstract: The blood-brain barrier (BBB) is created by a combination of endothelial cells with tight junctions and astrocytes. One of the key tight junction proteins, zona occludens-1 (ZO-1), has been reported to be stimulated in its expression by insulin and IGF-1. To assess the role of insulin and IGF-1 in endothelial cells in the BBB we have utilized mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) and IGF-1 receptor (VENIFARKO). Both of these mice show a normal BBB based on no increase in leakage of Evans blue dye in the brain of these mice basally or after cold injury. Furthermore, the structural integrity of the BBB and blood-retinal barrier (BRB) was intact using the vascular markers lectin B-4 and ZO-1, and both proteins were properly co-localized in both brain and retinal vascular tissue of these mice. These observations indicate that neither insulin nor IGF-1 signaling in vascular endothelial cells is required for development and maintenance of BBB or BRB.
authors.affiliation: Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
authors.forename: Kennard
authors.initials: K
authors.lastname: Thomas
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D003080:Cold Temperature / Q000009:adverse effects; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017526:Receptor, IGF Type 1 / Q000172:deficiency*; D011972:Receptor, Insulin / Q000172:deficiency*; D015398:Signal Transduction; D014018:Tissue Distribution
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin