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Diabetes. 2011 Mar;60(3):876-83. doi: 10.2337/db10-0793. Epub 2011 Feb 9.

Glucose and inflammation control islet vascular density and beta-cell function in NOD mice: control of islet vasculature and vascular endothelial growth factor by glucose.

Author information

  • 1Department of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. eitan.akirav@yale.edu

Abstract

OBJECTIVE:

β-Cell and islet endothelial cell destruction occurs during the progression of type 1 diabetes, but, paradoxically, β-cell proliferation is increased during this period. Altered glucose tolerance may affect β-cell mass and its association with endothelial cells. Our objective was to study the effects of glucose and inflammation on islet vascularity and on β function, mass, and insulin in immunologically tolerant anti-CD3 monoclonal antibody (mAb)-treated and prediabetic NOD mice.

RESEARCH DESIGN AND METHODS:

The effects of phloridzin or glucose injections on β-cells and endothelial cells were tested in prediabetic and previously diabetic NOD mice treated with anti-CD3 mAbs. Glucose tolerance, immunofluorescence staining, and examination of islet cultures ex vivo were evaluated.

RESULTS:

Islet endothelial cell density decreased in NOD mice and failed to recover after anti-CD3 mAb treatment despite baseline euglycemia. Glucose treatment of anti-CD3 mAb-treated mice showed increased islet vascular density and increased insulin content, which was associated with improved glucose tolerance. The increase in the vascular area was dependent on islet inflammation. Increased islet endothelial cell density was associated with increased production of vascular endothelial growth factor (VEGF) by islets from NOD mice. This response was recapitulated ex vivo by the transfer of supernatants from NOD islets cultured in high-glucose levels.

CONCLUSIONS:

Our results demonstrate a novel role for glucose and inflammation in the control of islet vasculature and insulin content of β-cells in prediabetic and anti-CD3-treated NOD mice. VEGF production by the islets is affected by glucose levels and is imparted by soluble factors released by inflamed islets.

PMID:
21307078
[PubMed - indexed for MEDLINE]
PMCID:
PMC3046848
Free PMC Article
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