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This version published online on January 26, 2006
Endocrinology, doi:10.1210/en.2005-0997
A more recent version of this article appeared on May 1, 2006
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Submitted on August 5, 2005
Accepted on January 18, 2006

ISLET ENDOTHELIAL CELLS AND PANCREATIC {beta}-CELL PROLIFERATION: STUDIES IN VITRO AND DURING PREGNANCY IN ADULT RATS

Magnus Johansson*, Göran Mattsson, Arne Andersson, Leif Jansson, and Per-Ola Carlsson

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; Biomedical Research Institute, Department of Biological Sciences, University of Warwick, Warwick, United Kingdom; Department of Medical Sciences, Uppsala University, Uppsala, Sweden

* To whom correspondence should be addressed. E-mail: Magnus.Johansson{at}medcellbiol.uu.se.

Growth of both tumors and nonneoplastic tissues may be influenced by signals from 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 the {beta}-cell proliferation in pregnant animals. Vascular growth was closely associated with the endocrine cell proliferation and prominent expression of HGF was observed in islet endothelium at day 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.
Key words: angiogenesis • beta-cell • pregnancy • proliferation • thrombospondin-1 • hepatocyte growth factor




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