Pancreatic Pancreatic β-Cell Replication: Relation to Insulin Secretion*

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Abstract
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 2 ways. In the presence of diazoxide (1-100 .mu.g/ml), insulin release was inhibited by as much as 86%, while the frequency of .beta.-cell replication was not reduced. In the presence of theophylline (1 mM), insulin release was increased by 23%, while .beta.-cell replication was inhibited. 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.