Format

Send to

Choose Destination
Cell Metab. 2014 Mar 4;19(3):498-511. doi: 10.1016/j.cmet.2014.02.001. Epub 2014 Feb 20.

Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes β cell regeneration.

Author information

1
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: marcela.brissova@vanderbilt.edu.
2
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
4
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA; Department of Biology, University of Alabama, Huntsville, Huntsville, AL 35899, USA.
5
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
6
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA. Electronic address: al.powers@vanderbilt.edu.

Erratum in

  • Cell Metab. 2015 Oct 6;22(4):750.

Abstract

Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After withdrawal of the VEGF-A stimulus, β cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing β cells. Bone marrow-derived macrophages (MΦs) 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. Identification of the signals responsible for the proliferation of adult, terminally differentiated β cells will improve strategies aimed at β cell regeneration and expansion.

PMID:
24561261
PMCID:
PMC4012856
DOI:
10.1016/j.cmet.2014.02.001
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center