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

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.