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

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). Further morel GLP-1R-/- islets exhibit abnormalities in cell topography, with two to threefold more centrally located a 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.