Conditional hypovascularization and hypoxia in islets do not overtly influence adult β cell mass and function

Joke D'Hoker, Nico De Leu, Yves Heremans, Luc Baeyens, Kohtaro Minami, Ying Cai, Astrid Marie-Therese Lavens, Marie Chintinne, Geert Stangé, Judith Magenheim, Avital Swisa, Geert Martens, Daniel Pipeleers, Mark Van De Casteele, Susumo Seino, Eli Keshet, Yuval Dor, Henry Heimberg

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
103 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)4165-4173
Number of pages9
JournalDiabetes
Volume62
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • beta cell mass

Fingerprint

Dive into the research topics of 'Conditional hypovascularization and hypoxia in islets do not overtly influence adult β cell mass and function'. Together they form a unique fingerprint.

Cite this