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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1827/-/DC1.
- Received December 26, 2012.
- Accepted August 14, 2013.
- © 2013 by the American Diabetes Association.
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