Islet formation during the neonatal development in mice

PLoS One. 2009 Nov 6;4(11):e7739. doi: 10.1371/journal.pone.0007739.


The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology / methods
  • Developmental Biology
  • Gene Expression Regulation, Developmental*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry / methods
  • Insulin-Secreting Cells / cytology*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / embryology*
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Models, Theoretical