Cyclic adenosine-3',5'-monophosphate stimulates islet B cell replication in neonatal rat pancreatic monolayer cultures

The Journal of Clinical Investigation
A RabinovitchD H Mintz

Abstract

A possible role for cyclic adenosine 3',5'-monophosphate (cAMP) in islet B cell replication was examined in neonatal rat pancreatic monolayer cultures. Islet cells deteriorated and insulin release decreased during 12 d of culture in medium with 5.6 mM glucose, whereas the cells survived and insulin release increased during culture in medium with 5.6 mM glucose plus the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM), or in medium with 16.7 mM glucose with or without IBMX. IBMX also increased the mitotic index and stimulated dose-dependent increases in [(3)H]thymidine incorporation in nuclei of islet B cells in aldehydethionine stained radioautographs; maximal stimulation of B cell replication occurred with addition of 0.1 mM IBMX to 5.6 mM glucose (+170%, P < 0.001), and this increase was similar to that observed with 16.7 mM glucose (+185%, P < 0.001). Also, 8-bromo-adenosine-3',5-monophosphate, but not 8-bromo-guanosine-3',5'-monophosphate produced dose-dependent increases in islet B cell replication in medium with 5.6 mM glucose. Measurement of cAMP levels in the cultures revealed dissociations between effects on B cell replication and insulin release. Thus, addition of 0.1 mM IBMX, or 0.1 nM cholera ...Continue Reading

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