β-cell replication and islet neogenesis following partial pancreatectomy

Partial pancreatectomy is one of the most commonly used models in the study of beta-cell regeneration. The mechanism by which regeneration occurs in this model has been controversial, with some claiming that islet and beta-cell neogenesis is important, while others claim that beta-cell replication is predominant. Here, we combined a time course analysis with continuous BrdU administration to study beta-cell regeneration following partial pancreatectomy. While exocrine cells in regenerating areas were highly proliferative and positive for BrdU, islets in regenerating areas were negative for BrdU one week after partial pancreatectomy, suggesting that they were derived from preexisting islets rather than being neogenic. The insulin-positive cells in ducts that have been reported by others and taken as evidence of beta-cell neogenesis were present in regenerating regions of the pancreas, but were relatively uncommon and were not highly proliferative, suggesting that they could not account for significant islet neogenesis. Consistent with a lack of islet neogenesis, regenerating areas following a second partial pancreatectomy were devoid of islets. beta-cell replication was detectable at a high frequency two weeks following partial pancreatectomy and was present at a similar frequency in both regenerating and preexisting regions of the pancreas. In summary, our data indicate that islet neogenesis following partial pancreatectomy does not occur.