Ductular cell proliferation in islet cell neogenesis induced by incomplete ligation of the pancreatic duct in dogs

Purpose. It has been suggested that islet neogenesis can be induced by incomplete ligation of the pancreatic duct in small animals; however, there has been no report of neogenesis and the proliferation of islets occurring in larger animals. When this procedure was performed in the Vervet monkey, it produced a noticeable increase in duct proliferation, but islet neogenesis was not observed, although the number of monkeys examined was very small. We conducted this study to evaluate whether islet neogenesis and ductular proliferation could be induced in larger animals such as the dog, by partial obstruction of the pancreatic duct. Methods. Incomplete ligation of the pancreatic duct was induced by tying the pancreas around the ventral side of the head with 2-0 silk and reducing the circumference by about 80% to cause partial obstruction. Results. By 2 weeks after ligation, we saw hyperplasia of the epithelial cells, multilayering of cuboidal cells, and proliferation of ductular cells. The terminal ductules involved in the formation of immunohistochemically insulin-positive islets, and islets, formed adjacent to the alignment of the ductular cells. By 8 weeks after ligation we saw scattered islets, less than 50 mum in diameter and less than 1 000 mum(2) in area. These cells were immunolabeled for both insulin and cytokeratin, and there was continuity between these insulin-positive cells and terminal ductular cells. Glucagon-positive cells and somatostatin-positive cells were also found adjacent to the alignment of ductular cells. Conclusions. These results suggest that islets may be differentiated from precursor cells in the pancreatic duct, and that stem cells exist even in adults.