Islet Endothelial Cells and Pancreatic β-Cell Proliferation: Studies in Vitro and during Pregnancy in Adult Rats

• Published in: Endocrinology (Philadelphia) 2006-05, Vol.147 (5), p.2315-2324
• Main Authors: Johansson, Magnus, Mattsson, Göran, Andersson, Arne, Jansson, Leif, Carlsson, Per-Ola
• Format: Article
• Language: English
• Subjects: Animals; Beta cells; Biological and medical sciences; Cell Proliferation; Cells, Cultured; Culture Media - metabolism; Culture Media, Conditioned - metabolism; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Growth factors; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Insulin-Secreting Cells - metabolism; Islets of Langerhans - cytology; Male; Microscopy, Fluorescence; Models, Biological; Pancreas; Physiological effects; Pregnancy; Pregnancy, Animal; Prolactin - metabolism; Rats; Rats, Wistar; Secretion; Sheep; Signal Transduction; Thrombospondin 1 - biosynthesis; Time Factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2005-0997

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 β-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 β-cells display a highly reproducible physiological proliferation. We show that islet endothelial cell proliferation precedes β-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 β-cell proliferation. In summary, our results suggest the existence of an endothelial-endocrine axis within adult pancreatic islets, which is of importance for adult β-cell proliferation.