Vascular Endothelial Growth Factor-A and Islet Vascularization Are Necessary in Developing, but Not Adult, Pancreatic Islets
- Rachel B. Reinert1,
- Marcela Brissova2,
- Alena Shostak2,
- Fong Cheng Pan3,
- Greg Poffenberger2,
- Qing Cai1,
- Gregory L. Hundemer2,
- Jeannelle Kantz1,
- Courtney S. Thompson2,
- Chunhua Dai2,
- Owen P. McGuinness1 and
- Alvin C. Powers1,2,4⇑
- 1Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
- 2Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
- 3Department of Cell and Developmental Biology and Vanderbilt University Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee
- 4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee
- Corresponding author: Alvin C. Powers, .
R.B.R. and M.B. contributed equally to this article.
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0071/-/DC1.
- Received January 15, 2013.
- Accepted July 19, 2013.
- © 2013 by the American Diabetes Association.
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