title: Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.
abstract: Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult β-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularization, leading to reduced β-cell proliferation in both developing and adult islets and, ultimately, reduced β-cell mass and impaired glucose clearance. When VEGF-A was inactivated in adult β-cells, islet vascularization was reduced twofold. Surprisingly, even after 3 months of reduced islet vascularization, islet architecture and β-cell gene expression, mass, and function were preserved with only a minimal abnormality in glucose clearance. These data show that normal pancreatic VEGF-A expression is critical for the recruitment of ECs and the subsequent stimulation of endocrine cell proliferation during islet development. In contrast, although VEGF-A is required for maintaining the specialized vasculature observed in normal adult islets, adult β-cells can adapt and survive long-term reductions in islet vascularity. These results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and β-cell mass.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Reinert
authors.forename: Marcela
authors.initials: M
authors.lastname: Brissova
authors.forename: Alena
authors.initials: A
authors.lastname: Shostak
authors.forename: Fong Cheng
authors.initials: FC
authors.lastname: Pan
authors.forename: Greg
authors.initials: G
authors.lastname: Poffenberger
authors.forename: Qing
authors.initials: Q
authors.lastname: Cai
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Hundemer
authors.forename: Jeannelle
authors.initials: J
authors.lastname: Kantz
authors.forename: Courtney S
authors.initials: CS
authors.lastname: Thompson
authors.forename: Chunhua
authors.initials: C
authors.lastname: Dai
authors.forename: Owen P
authors.initials: OP
authors.lastname: McGuinness
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000098:blood supply* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D005947:Glucose