Pancreatic Islet Vasculature Adapts to Insulin Resistance Through Dilation and Not Angiogenesis

  1. Alvin C. Powers1,3,5
  1. 1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  2. 2Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
  3. 3Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
  4. 4Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  5. 5Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
  1. Corresponding author: Alvin C. Powers, al.powers{at}
  1. C.D. and M.B. contributed equally to this work.


Pancreatic islets adapt to insulin resistance through a complex set of changes, including β-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4+/−, and mice with high-fat diet–induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the β-cell core but not in the islet periphery. Intraislet endothelial cell fenestration, proliferation, and islet angiogenic factor/receptor expression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. We propose that the islet capillary dilation is modulated by endothelial nitric oxide synthase via complementary signals derived from β-cells, parasympathetic nerves, and increased islet blood flow. These compensatory changes in islet vascularization may influence whether β-cells can adequately respond to insulin resistance and prevent the development of diabetes.


  • Received November 30, 2012.
  • Accepted April 17, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents

This Article

  1. Diabetes vol. 62 no. 12 4144-4153
  1. Supplementary Data
  2. All Versions of this Article:
    1. db12-1657v1
    2. 62/12/4144 most recent