Pancreatic beta-cell replication: relation to insulin secretion.

The relationship between beta-cell replication and insulin release was investigated utilizing neonatal rat pancreatic monolayer cell cultures. Glucose-induced insulin release was either inhibited using diazoxide or mannoheptulose, or potentiated using theophylline. The corresponding effects on the frequency of beta-cell replication were determined by incubating cultures with [3H]thymidine and estimating the frequency of beta-cell labeling in aldehyde thionine-stained radioautographs. beta-Cell replication and insulin release were shown to be dissociable processes in two ways. First, in the presence of diazoxide (1-100 microgram/ml), insulin release was inhibited by as much as 86%, while the frequency of beta-cell replication was not reduced. Second, in the presence of theophylline (1 mM), insulin release was increased by 23%, while beta-cell replication was inhibited. Finally, the inhibition of both beta-cell replication and insulin release by mannoheptulose (5.5 mM) indicated that glucose utilization may be important for both of these beta-cell processes.