Cyclic Adenosine-3′,5′ -monophosphate Stimulates Islet B Cell Replication in Neonatal Rat Pancreatic Monolayer Cultures

AUTOR(ES)

Rabinovitch, Alexander

RESUMO

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 [3H]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 toxin, to 5.6 mM glucose produced slightly greater increases in cAMP levels and B cell replication than did 16.7 mM glucose, whereas insulin release was increased significantly more with 16.7 mM glucose. Also, addition of 0.1 mM IBMX, or 0.1 nM cholera toxin, to 16.7 mM glucose stimulated further increases in cAMP levels and insulin release in the cultures, but no further increases in B cell replication. We conclude that (a) cAMP stimulates islet B cell replication, (b) cAMP may mediate the effects of glucose on B cell replication, and (c) mechanisms regulating B cell replication may be more sensitive to cAMP and/or different from those regulating insulin secretion.

Documentos Relacionados

• An Effect of Dexamethasone on Adenosine 3′,5′ -Monophosphate Content and Adenosine 3′,5′ -Monophosphate Phosphodiesterase Activity of Cultured Hepatoma Cells
• Renal effects of adenosine 3′,5′-cyclic monophosphate and dibutyryl adenosine 3′,5′-cyclic monophosphate: Evidence for a role for adenosine 3′,5′-cyclic monophosphate in the regulation of proximal tubular sodium reabsorption
• Cyclic Adenosine 3′,5′-Monophosphate in Escherichia coli
• Adenosine 3',5'-cyclic monophosphate in Vibrio cholerae.
• Adenosine 3′:5′-cyclic monophosphate- and guanosine 3′:5′-cyclic monophosphate-dependent protein kinases: Possible homologous proteins