Vascular Endothelial Growth Factor-A and Islet Vascularization Are Necessary in Developing, but Not Adult, Pancreatic Islets

  1. Alvin C. Powers1,2,4
  1. 1Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
  2. 2Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  3. 3Department of Cell and Developmental Biology and Vanderbilt University Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee
  4. 4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee
  1. Corresponding author: Alvin C. Powers, al.powers{at}vanderbilt.edu.
  1. R.B.R. and M.B. contributed equally to this article.

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.

Footnotes

  • Received January 15, 2013.
  • Accepted July 19, 2013.

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  1. Diabetes vol. 62 no. 12 4154-4164
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