[PDF][PDF] Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes β cell regeneration

M Brissova, K Aamodt, P Brahmachary, N Prasad… - Cell metabolism, 2014 - cell.com
M Brissova, K Aamodt, P Brahmachary, N Prasad, JY Hong, C Dai, M Mellati, A Shostak…
Cell metabolism, 2014cell.com
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 …
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.
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