Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats

Endocrinology. 2006 May;147(5):2315-24. doi: 10.1210/en.2005-0997. Epub 2006 Jan 26.


The growth of both tumors and nonneoplastic tissues may be influenced by signals from the vascular endothelium. In the present investigation we show that purified proliferating endothelial cells from pancreatic islets can stimulate beta-cell proliferation through secretion of hepatocyte growth factor (HGF). This secretion could be induced by soluble signals from the islets, such as vascular endothelial growth factor-A (VEGF-A) and insulin. During pregnancy, the pancreatic beta-cells display a highly reproducible physiological proliferation. We show that islet endothelial cell proliferation precedes beta-cell proliferation in pregnant animals. Vascular growth was closely associated with endocrine cell proliferation, and prominent expression of HGF was observed in islet endothelium on d 15 of pregnancy, i.e. coinciding with the peak of beta-cell proliferation. In summary, our results suggest the existence of an endothelial-endocrine axis within adult pancreatic islets, which is of importance for adult beta-cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media / metabolism
  • Culture Media, Conditioned / metabolism
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Hepatocyte Growth Factor / metabolism
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / cytology*
  • Male
  • Microscopy, Fluorescence
  • Models, Biological
  • Pregnancy
  • Pregnancy, Animal
  • Prolactin / metabolism
  • Rats
  • Rats, Wistar
  • Sheep
  • Signal Transduction
  • Thrombospondin 1 / biosynthesis
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism


  • Culture Media
  • Culture Media, Conditioned
  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A
  • Hepatocyte Growth Factor
  • Prolactin