EXPRESSION OF NEURAL CELL-ADHESION MOLECULE (N-CAM) IN RAT ISLETS ANDITS ROLE IN ISLET-CELL TYPE SEGREGATION

Endocrine cell types are non-randomly distributed within pancreatic is lets of Langerhans; In the rat, insulin-secreting B-cells occupy the c ore of the islets and are surrounded by A-, D- and PP-cells, secreting glucagon, somatostatin and pancreatic polypeptide, respectively. Furt hermore, dissociated islet cells have the ability in vitro to form agg regates with the same cell-type organization as native islets (pseudoi slets). These observations suggest that a differential expression of c ell adhesion molecules (CAMs) might characterize B- and non-B-cells (A -, D- and PP-cells), and be in part responsible for the establishment and maintenance of islet architecture. Indirect immunofluorescence usi ng antibodies against CAMs and islet hormones was performed on serial sections of the splenic and duodenal parts of the rat pancreas. Staini ng for the Ca2+-dependent CAM E-cadherin was detected on both exocrine and endocrine tissue and was uniform over the entire islet section, i n both pancreatic regions. By contrast, staining for the Ca2+-independ ent neural CAM (N-CAM) was restricted to endocrine tissue and nerve en dings. Furthermore, N-CAM staining of endocrine cells was stronger in the islet periphery, a region composed mostly of non-B-cells. Serial s ections demonstrate that cells staining strongly for N-CAM in the sple nic part correspond to glucagon cells and in the duodenal part to panc reatic polypeptide cells. Within pseudoislets in vitro a stronger stai ning for N-CAM was also observed on peripheral cells, corresponding to non-B-cells. These data suggest that a difference in the expression o f N-CAM might play a role in the segregation between islet cells. To v erify this hypothesis, isolated islet cells were allowed to form aggre gates in culture, in the presence of non-immune or anti-N-CAM Fab frag ments. Inhibition of N-CAM function by specific Fab fragments prevente d the segregation between cell types that normally occurs within 5 day s. In conclusion, higher levels of N-CAM characterize peripheral islet s cells, irrespective of their secretory type, and anti-N-CAM Fab frag ments prevent islet cell type segregation within pseudoislets in vitro . These results suggest that differences in N-CAM expression between c ell types contribute to the characteristic distribution of cells withi n islets of Langerhans.