title: Conditional hypovascularization and hypoxia in islets do not overtly influence adult β-cell mass or function.
abstract: It is generally accepted that vascularization and oxygenation of pancreatic islets are essential for the maintenance of an optimal β-cell mass and function and that signaling by vascular endothelial growth factor (VEGF) is crucial for pancreas development, insulin gene expression/secretion, and (compensatory) β-cell proliferation. A novel mouse model was designed to allow conditional production of human sFlt1 by β-cells in order to trap VEGF and study the effect of time-dependent inhibition of VEGF signaling on adult β-cell fate and metabolism. Secretion of sFlt1 by adult β-cells resulted in a rapid regression of blood vessels and hypoxia within the islets. Besides blunted insulin release, β-cells displayed a remarkable capacity for coping with these presumed unfavorable conditions: even after prolonged periods of blood vessel ablation, basal and stimulated blood glucose levels were only slightly increased, while β-cell proliferation and mass remained unaffected. Moreover, ablation of blood vessels did not prevent β-cell generation after severe pancreas injury by partial pancreatic duct ligation or partial pancreatectomy. Our data thus argue against a major role of blood vessels to preserve adult β-cell generation and function, restricting their importance to facilitating rapid and adequate insulin delivery.
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Joke
authors: J
authors: D'Hoker
authors: Nico
authors: N
authors: De Leu
authors: Yves
authors: Y
authors: Heremans
authors: Luc
authors: L
authors: Baeyens
authors: Kohtaro
authors: K
authors: Minami
authors: Cai
authors: C
authors: Ying
authors: Astrid
authors: A
authors: Lavens
authors: Marie
authors: M
authors: Chintinne
authors: Geert
authors: G
authors: Stangé
authors: Judith
authors: J
authors: Magenheim
authors: Avital
authors: A
authors: Swisa
authors: Geert
authors: G
authors: Martens
authors: Daniel
authors: D
authors: Pipeleers
authors: Mark
authors: M
authors: van de Casteele
authors: Susumo
authors: S
authors: Seino
authors: Eli
authors: E
authors: Keshet
authors: Yuval
authors: Y
authors: Dor
authors: Harry
authors: H
authors: Heimberg
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
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