Dissociation between insulin secretion and DNA synthesis in cultured pancreatic islets

Glucose has been suggested to be the most important stimulus for beta cell replication in vivo and in vitro. In order to study the relationship between insulin secretion and DNA synthesis, newborn rat islets were cultured in the presence of different concentrations of glucose, theophylline and 3-isobutyl-1-methylxanthine (IBMX). DNA synthesis was evaluated by the incorporation of [3H]thymidine (3H-Tdr) into islet DNA, and the release of insulin and the content of insulin and DNA in the islets were determined. No difference in 3H-Tdr incorporation was observed after 24 h culture in 5.5, 11 and 22 mM glucose in spite of a dose dependent increase in insulin release. 5 mM theophylline potentiated the glucose induced insulin release but lowered both 3H-Tdr synthesis and insulin content in the islets. In contrast, 0.05 mM IBMX induced a significant stimulation of both insulin release and 3H-Tdr incorporation. However, long-term exposure to IBMX did not result in increased DNA content of the islets. Inhibition of the DNA synthesis by 5 mM hydroxyurea resulted in a marked reduction in DNA content of the islets but no decrease in either insulin release or insulin content when expressed per ng DNA. These results indicate that insulin secretion and DNA synthesis can be dissociated and may suggest participation of factors other than glucose in the control of beta cell replication.