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ABSTRACT Endocrine cell types are non-randomly distributed within pancreatic islets of Langerhans. In the rat, insulin- secreting B-cells occupy the core of the islets and are sur- rounded by A-, D- and PP-cells, secreting glucagon, somatostatin and pancreatic polypeptide, respectively. Furthermore, dissociated islet cells have the ability in vitro to form aggregates with the same cell-type organization as native islets (pseudoislets). These observations suggest that a differential expression of cell adhesion molecules (CAMs) might characterize B- and non-B-cells (A-, D- and PP-cells), and be in part responsible for the establishment and main- tenance of islet architecture. Indirect immunofluorescence using antibodies against CAMs and islet hormones was performed on serial sections of the splenic and duodenal parts of the rat pancreas. Staining for the Ca2+-dependent CAM E-cadherin was detected on both exocrine and endocrine tissue and was uniform over the entire islet section, in both pancreatic regions. By contrast, staining for the Ca2+-independent neural CAM (N-CAM) was restricted to endocrine tissue and nerve endings. Further- more, N-CAM staining of endocrine cells was stronger in the islet periphery, a region composed mostly of non-B-cells. Serial sections demonstrate that cells staining strongly for N-CAM in the splenic part correspond to glucagon cells and in the duodenal part to pancreatic polypeptide cells. Within pseudoislets in vitro a stronger staining for N-CAM was also observed on peripheral cells, corresponding to non-B-cells.These data suggest that a dif- ference in the expression of N-CAM might play a role in the segregation between islet cells. To verify this hypothe- sis, isolated islet cells were allowed to form aggregates in culture, in the presence of non-immune or anti-N-CAM Fab fragments. Inhibition of N-CAM function by specific Fab fragments prevented the segregation between cell types that normally occurs within 5 days. In conclusion, higher levels of N-CAM characterize peripheral islets cells, irrespective of their secretory type, and anti-N-CAM Fab fragments prevent islet cell type segregation within pseudoislets in vitro. These results suggest that differences in N-CAM expression between cell types contribute to the characteristic distribution of cells within islets of Langer- hans.
Cirulli et al. (Wed,) studied this question.