Blood vessels of human islets of Langerhans are surrounded by a double basement membrane

Diabetologia. 2008 Jul;51(7):1181-91. doi: 10.1007/s00125-008-0997-9. Epub 2008 Apr 26.


Aims/hypothesis: Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive.

Methods: Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution.

Results: Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which co-invaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm alpha5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR, whereas alpha(3) and beta(1) integrins were more diffusely distributed. High Lutheran content was also found on endocrine cell membranes in short-term culture of human islets. The adhesion of dispersed beta cells to Lm-511 was inhibited equally effectively by antibodies to integrin and alpha(3) and beta(1) subunits, and by soluble Lutheran peptide.

Conclusions/interpretation: The present results disclose a hitherto unrecognised BM organisation and adhesion mechanisms in human pancreatic islets as distinct from mouse islets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal
  • Basement Membrane / cytology*
  • Basement Membrane / metabolism
  • Basement Membrane / ultrastructure
  • Biomarkers / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Endocrine System / cytology
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Humans
  • Immunohistochemistry
  • Islets of Langerhans / blood supply*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / ultrastructure
  • Laminin / immunology
  • Laminin / metabolism
  • Lutheran Blood-Group System
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microscopy, Electron, Transmission
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism
  • Receptors, Laminin / immunology
  • Receptors, Laminin / metabolism


  • Antibodies, Monoclonal
  • BCAM protein, human
  • Bcam protein, mouse
  • Biomarkers
  • Cell Adhesion Molecules
  • Laminin
  • Lutheran Blood-Group System
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Receptors, Laminin
  • laminin alpha5