Islet neogenesis is stimulated by brief occlusion of the main pancreatic duct.

OBJECTIVE Current models of islet neogenesis either cause substantial pancreatic damage or continuously stimulate the pancreas, making these models unsuitable for the study of early events that occur in the neogenic process. We aimed to develop a method where the initial events that culminate in increased pancreatic endocrine mass can be studied. DESIGN AND METHODS Ten 12-week-old female Wistar rats were subjected to a midline laparotomy, the pancreas was isolated and the main pancreatic duct was occluded for 60 seconds. The pancreas was released and carefully relocated within the abdomen. Ten age-, strain- and sex-matched control rats were subjected to a sham operation. The animals were killed 56 days post occlusion, and the pancreata excised and fixed for histological analysis. Body, pancreatic and hepatic weights were noted at termination and serum was taken for analysis. The endocrine-to-exocrine ratio was calculated and the number of endocrine cells in each islet from the sectioned pancreata was counted. RESULTS Occlusion of the main pancreatic duct for 60 seconds results in an increase in endocrine mass by 80% 56 days post occlusion. This constitutes an increase in endocrine units (1-6 cells), and in small (7-30 cells), medium (31-60 cells) and large (> 60 cells) islets by 85%, 96%, 95% and 71% respectively. CONCLUSION Brief occlusion of the main pancreatic duct results in an increase in pancreatic endocrine mass. An increase in endocrine units and small islets is indicative of islet neogenesis. Therefore, owing to the briefness of the stimulation, this model can therefore be used to study the initial events that occur during the neogenic process.