Atrial Natriuretic Peptide (Anp) And Islet Beta-Cell Growth

Atrial natriuretic peptide (ANP) is a stimulus for particulate guanylyl cyclase and cyclic GMP (cGMP) formation through natriuretic peptide receptors A and B. Natriuretic peptide receptor subtypes A, B, and C mRNAs were identified by RT‐PCR in rat pancreatic islets of Langerhans. Culture of isolated rat islets at 5.5 mM glucose with ANP (1 M) for 7 days resulted in increased [ 3 H]thymidine incorporation that was 200±36% of control (P<0.05). Rat insulinoma INS‐1e cell [ 3 H]thymidine incorporation were similarly stimulated by ANP to 163±18% (P<0.05) of control. 8‐Bromo‐cGMP (0.5 mM) also stimulated islet [ 3 H]thymidine incorporation to 207±15% of control (P<0.001). The expression of cyclin D2 mRNA was also increased by ANP. The total protein content of INS‐1e cells did not change during ANP stimulation. The total insulin content of pancreatic islets did not change during 7 day culture with ANP. However, the islet insulin secretory response to 11 mM glucose was markedly inhibited (74±7%) (P<0.01) by ANP after 7 day culture (but not a 3 hour pretreatment). Thus, ANP stimulates a mitogenic response in islets and INS‐1 cells that can be mimicked by cGMP. Long‐term ANP treatment also blunts the β‐cell insulin secretory response to glucose, but does not significantly alter total insulin content.