Authors:
Marcela Brissova, Kristie Aamodt, Priyanka Brahmachary, Nripesh Prasad, Ji-Young Hong, Chunhua Dai, Mahnaz Mellati, Alena Shostak, Greg Poffenberger, Radhika Aramandla, Shawn E. Levy, & Alvin C. Powers
Summary:
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 β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After withdrawal of the VEGF-A stimulus, β cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing β cells. Bone marrow-derived macrophages (MΦs) recruited to the site of β cell injury were crucial for the β 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 β cells will improve strategies aimed at β cell regeneration and expansion.
Source:
Cell Metabolism; Vol. 19, Issue 3, 498-511 (03/04/14)