Conditional hypovascularization and hypoxia in islets do not overtly influence adult b-cell mass or function

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

It is generally accepted that vascularization and oxygenation of pancreatic islets are essential for the maintenance of an optimal b-cell mass and function and that signaling by vascular endothelial growth factor (VEGF) is crucial for pancreas development, insulin gene expression/secretion, and (compensatory) b-cell proliferation. A novel mouse model was designed to allow conditional production of human sFlt1 by b-cells in order to trap VEGF and study the effect of time-dependent inhibition of VEGF signaling on adult b-cell fate and metabolism. Secretion of sFlt1 by adult b-cells resulted in a rapid regression of blood vessels and hypoxia within the islets. Besides blunted insulin release, b-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 b-cell proliferation and mass remained unaffected. Moreover, ablation of blood vessels did not prevent b-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 b-cell generation and function, restricting their importance to facilitating rapid and adequate insulin delivery.

Original languageAmerican English
Pages (from-to)4165-4173
Number of pages9
JournalDiabetes
Volume62
Issue number12
DOIs
StatePublished - Dec 2013

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