Increase of beta cell mass by beta cell replication, but not neogenesis, in the maternal pancreas in mice.

Strategies for increasing functional beta cell mass are effective for diabetes therapy. Although controversy remains on the existence of facultative beta cell progenitors in the adult pancreas, most evidence does not support such a possibility. One of the greatest physiological increases in beta cells has been detected in the maternal pancreas during pregnancy, following neonatal period and in the setting of insulin resistance. However, no systematical analysis on the beta cell growth in this period has been ever performed. Here we analyzed beta cell replication by quantifying BrdU incorporated beta cells at different time points in the pregnant mice. Similarly, we evaluated the possible involvement of beta cell neogenesis (differentiation from progenitor cells) by analyzing expression of Neurog3, a key determinant of pancreatic endocrine cell neogenesis during embryogenesis, in the exocrine pancreas. We found a dynamic increase in beta cell replication, but failed to detect beta cell neogenesis, demonstrating that beta cell growth in the maternal pancreas during pregnancy is predominantly attributable to beta cell replication, rather than beta cell neogenesis.