Vascular Endothelial Growth Factor-A and Islet Vascularization Are Necessary in Developing, but Not Adult, Pancreatic Islets
Rachel B. Reinert,Marcela Brissova,Alena Shostak,Fong Cheng Pan,Greg Poffenberger,Qing Cai,Gregory L. Hundemer,Jeannelle Kantz,Courtney S. Thompson,Chunhua Dai,Owen P. McGuinness,Alvin C. Powers,Alvin C. Powers +12 more
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TLDR
Results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and β-cell mass, and that adult β-cells can adapt and survive long-term reductions in isletascularity.Abstract:
Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult β-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularization, leading to reduced β-cell proliferation in both developing and adult islets and, ultimately, reduced β-cell mass and impaired glucose clearance. When VEGF-A was inactivated in adult β-cells, islet vascularization was reduced twofold. Surprisingly, even after 3 months of reduced islet vascularization, islet architecture and β-cell gene expression, mass, and function were preserved with only a minimal abnormality in glucose clearance. These data show that normal pancreatic VEGF-A expression is critical for the recruitment of ECs and the subsequent stimulation of endocrine cell proliferation during islet development. In contrast, although VEGF-A is required for maintaining the specialized vasculature observed in normal adult islets, adult β-cells can adapt and survive long-term reductions in islet vascularity. These results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and β-cell mass.read more
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Islet Microenvironment, Modulated by Vascular Endothelial Growth Factor-A Signaling, Promotes β Cell Regeneration
Marcela Brissova,Kristie Aamodt,Priyanka Brahmachary,Nripesh Prasad,Ji-Young Hong,Chunhua Dai,Mahnaz Mellati,Alena Shostak,Greg Poffenberger,Radhika Aramandla,Shawn Levy,Alvin C. Powers +11 more
TL;DR: Bone marrow-derived macrophages 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.
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Regulation of tissue morphogenesis by endothelial cell-derived signals.
TL;DR: Endothelial cells are emerging as important signaling centers that coordinate regeneration and help to prevent deregulated, disease-promoting processes in the regulation of organ morphogenesis, maintenance, and regeneration.
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Signals in the pancreatic islet microenvironment influence β-cell proliferation.
TL;DR: This review highlights different components of the pancreatic microenvironment, and reviews what is known about how signaling that occurs between β‐cells and these other components influences β‐cell proliferation.
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The β-Cell/EC Axis: How Do Islet Cells Talk to Each Other?
Heshan Peiris,Claudine S. Bonder,P. Toby Coates,P. Toby Coates,Damien J. Keating,Claire F. Jessup,Claire F. Jessup +6 more
TL;DR: The evidence supporting the intraislet EC as an important partner for β-cell function is examined to highlight the relevance of this axis in the context of type 1 and type 2 diabetes.
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Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes
Marcela Brissova,Alena Shostak,Corinne L. Fligner,Frank Revetta,Mary Kay Washington,Alvin C. Powers,Rebecca L. Hull +6 more
TL;DR: It is found that human islets have five-fold fewer vessels per islet area than mouse islets, and changes in islet vasculature in T2D islets appeared to be associated with amyloid deposition, which was noted in islets from 8/9 T1D subjects.
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