title: Modulation of endoglin expression in islets of langerhans by VEGF reveals a novel regulator of islet endothelial cell function.
abstract: BACKGROUND
  Endoglin/CD105 is an auxiliary receptor for transforming growth factor-β with established roles in vascular remodelling. It has recently been shown that heterozygous endoglin deficiency in mice decreases insulin secretion in an animal model of obesity, highlighting a potential role for endoglin in the regulation of islet function. We have previously identified two different populations of endoglin expressing cells in human and mouse islets which are: (i) endothelial cells (ECs) and (ii) islet mesenchymal stromal cells. The contribution of islet EC endoglin expression to islet development and sensitivity to VEGF is unknown and is the focus of this study.
  
  
  RESULTS
  In vitro culture of mouse islets with VEGF164 for 48 h increased endoglin mRNA levels above untreated controls but VEGF did not modulate VEGFR2, CD31 or CD34 mRNA expression or islet viability. Removal of EC-endoglin expression in vivo reduced islet EC area but had no apparent effect on islet size or architecture.
  
  
  CONCLUSIONS
  EC-specific endoglin expression in islets is sensitive to VEGF and plays partial roles in driving islet vascular development, however such regulation appears to be distinct to mechanisms required to modulate islet viability and size.
authors.affiliation: Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, Kings College London, London, SE1 1UL, UK. C.E.Clarkin@soton.ac.uk.|Centre for Biological Sciences, University of Southampton, Building 85/Life Sciences, University Road, Southampton, SO17 1BJ, UK. C.E.Clarkin@soton.ac.uk.
authors.forename: Claire E
authors.identifier: http://orcid.org/0000-0001-6859-5897
authors.initials: CE
authors.lastname: Clarkin
authors.affiliation: Institute of Genetic Medicine, Newcastle University, London, NE1 3BZ, UK.
authors.forename: Marwa
authors.initials: M
authors.lastname: Mahmoud
authors.affiliation: Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, Kings College London, London, SE1 1UL, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85/Life Sciences, University Road, Southampton, SO17 1BJ, UK.
authors.forename: Emmanuel O
authors.initials: EO
authors.lastname: Sobamowo
authors.affiliation: Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, Kings College London, London, SE1 1UL, UK.
authors.forename: Aileen
authors.initials: A
authors.lastname: King
authors.affiliation: Institute of Genetic Medicine, Newcastle University, London, NE1 3BZ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Arthur
authors.affiliation: Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, Kings College London, London, SE1 1UL, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
authors.affiliation: Comparative Biomedical Sciences, The Royal Veterinary College, London, NW1 0TU, UK.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Wheeler-Jones
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D000071063:Endoglin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D000071063:Endoglin; C502004:Eng protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Endoglin; Hypoxia inducible factor-1 alpha; Islets; VEGF