Atrial Natriuretic Peptide Affects Stimulus-Secretion Coupling of Pancreatic β-Cells

Atrial natriuretic peptide (ANP) potentiated the effect of glucagon-like peptide 1 (GLP-1) on glucose-induced insulin secretion, most likely through cGMP-mediated inhibition of PDE3B, which reduces cAMP degradation. This study evaluated the effects of ANP on β-cell function using a β-cell–specific knockout of the ANP receptor (βGC-A-KO), demonstrating that ANP acts through the GC-A receptor to augment insulin secretion and decrease K-ATP channel activity at threshold glucose concentrations. These effects were absent in βGC-A-KO mice, confirming GC-A receptor dependence. The findings point to a dual mechanism — the cGMP/PKG and cAMP/PKA/Epac pathways — through which ANP regulates β-cell function and links cardiovascular and metabolic signaling. (Diabetes. 2017;66:2840–2848. DOI: 10.2337/db17-0392.)