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

Brissova M, Aamodt K, Brahmachary P, Prasad N, Hong JY, Dai C, Mellati M, Shostak A, Poffenberger G, Aramandla R, Levy SE, Powers AC
Cell Metab. 2014 19 (3): 498-511

PMID: 24561261 · PMCID: PMC4012856 · DOI:10.1016/j.cmet.2014.02.001

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (19)

Animals Antibiotics, Antineoplastic Cell Differentiation Cell Proliferation Doxorubicin Endothelial Cells Gene Expression Profiling Humans Insulin-Secreting Cells Islets of Langerhans Islets of Langerhans Transplantation Leukocyte Common Antigens Macrophages Mice Mice, Inbred C57BL Mice, Transgenic Regeneration Signal Transduction Vascular Endothelial Growth Factor A

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