Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
Diane C. Saunders,
Kristie I. Aamodt,
Tiffany M. Richardson,
David K Flaherty,
Shawn E. Levy,
Alvin C. Powers,
Posted 30 Aug 2020
bioRxiv DOI: 10.1101/2020.08.28.265728
Posted 30 Aug 2020
Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal. ### Competing Interest Statement The authors have declared no competing interest.
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