Glucagon-like peptide 1 receptor signaling influences topography of islet cells in mice

Virchows Arch. 2001 Apr;438(4):382-7. doi: 10.1007/s004280000374.


Glucagon-like peptide 1 (GLP-1) amplifies glucose-induced insulin release in vivo and in vitro. Activation of GLP-1 receptor (GLP-1R) signaling leads to differentiation of exocrine cells towards a beta-cell phenotype in vitro and stimulation of islet cell proliferation in vitro and in vivo, suggesting a potential role for GLP-1 in the modulation of islet growth and differentiation. To determine whether basal levels of GLP-1R signaling are essential for islet development, we examined islet cell composition and topography in GLP-1R-/- mice. Total beta-cell volume and number are not altered, but the topography of beta cells is markedly different in GLP-1R-/- mice compared with GLP-1R+/+ controls. The distribution of beta cells is shifted from large to small and medium-sized islets in the absence of GLP-1R signaling (large islets: 50 +/- 3% in GLP-1R+/+ vs 28 +/- 4% in GLP- 1R-/-, P < 0.01 and medium islets: 32 +/- 2% in GLP- 1R+/+ vs 48 +/- 3% in GLP-1R-/-, P < 0.001). Furthermore, GLP-1R-/- islets exhibit abnormalities in cell topography, with two to threefold more centrally located alpha cells detected in GLP-1R-/- islets. These alterations in alpha- and beta-cell topography indicate that basal levels of GLP-1 signaling in the normal rodent are involved in the normal cellular organization of the endocrine pancreas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • Insulin / metabolism
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Peptide Fragments / metabolism*
  • Protein Precursors / metabolism*
  • Signal Transduction
  • Specific Pathogen-Free Organisms
  • Tissue Distribution


  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon