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Diabetes. 2013 Dec;62(12):4165-73. doi: 10.2337/db12-1827. Epub 2013 Aug 23.

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

Author information

1
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.

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.

PMID:
23974922
PMCID:
PMC3837025
DOI:
10.2337/db12-1827
[Indexed for MEDLINE]
Free PMC Article

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