Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes ? cell regeneration.

ABSTRACT: Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment, and ? cell mass, we transiently increased VEGF-A production by ? cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to ? cell loss. After withdrawal of the VEGF-A stimulus, ? cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing ? cells. Bone marrow-derived macrophages (M?s) recruited to the site of ? cell injury were crucial for the ? cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated ? cells will improve strategies aimed at ? cell regeneration and expansion.

SUBMITTER: Brissova M 

PROVIDER: S-EPMC4012856 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature